Sample records for leukemia nuclear bodies

  1. A Bayesian Network Model of Proteins' Association with Promyelocytic Leukemia (PML) Nuclear Bodies

    E-print Network

    Dellaire, Graham

    A Bayesian Network Model of Proteins' Association with Promyelocytic Leukemia (PML) Nuclear Bodies. Promyelocytic leukemia nuclear bodies are implicated in important regulatory processes. To understand leukemia nuclear bodies accurately when interaction data is available. At a false positive rate of 10

  2. Arsenic-Induced PML Targeting onto Nuclear Bodies: Implications for the Treatment of Acute Promyelocytic Leukemia

    Microsoft Academic Search

    Jun Zhu; Marcel H. M. Koken; Frederique Quignon; Mounira K. Chelbi-Alix; Laurent Degos; Zhen Yi Wang; Zhu Chen; Hugues de The

    1997-01-01

    Acute promyelocytic leukemia (APL) is associated with the t(15;17) translocation, which generates a PML\\/RARalpha fusion protein between PML, a growth suppressor localized on nuclear matrix-associated bodies, and RARalpha , a nuclear receptor for retinoic acid (RA). PML\\/RARalpha was proposed to block myeloid differentiation through inhibition of nuclear receptor response, as does a dominant negative RARalpha mutant. In addition, in APL

  3. Trafficking of the Transcription Factor Nrf2 to Promyelocytic Leukemia-Nuclear Bodies

    PubMed Central

    Malloy, Melanie Theodore; McIntosh, Deneshia J.; Walters, Treniqka S.; Flores, Andrea; Goodwin, J. Shawn; Arinze, Ifeanyi J.

    2013-01-01

    Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is an extensively studied mechanism for regulating the cellular level of Nrf2. Although mechanistic details are lacking, reports abound that Nrf2 can also be degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3-modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key components of PML-NBs did not contain biologically active Keap1 but contained modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3 ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML-NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this decrease, resulting in elevated levels of polysumoylated Nrf2 that was also ubiquitylated. Wild-type RNF4 accelerated the half-life (t½) of Nrf2, measured in PML-NB-enriched cell fractions. These results suggest that RNF4 mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for sumoylation and provides a novel mechanism for its degradation in the nucleus, independent of Keap1. PMID:23543742

  4. Acute promyelocytic leukemia, arsenic, and PML bodies

    PubMed Central

    Le Bras, Morgane; Lallemand-Breitenbach, Valérie

    2012-01-01

    Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor ? (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation. PMID:22778276

  5. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

    SciTech Connect

    Sides, Mark D. [Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA (United States); Block, Gregory J. [University of Washington Institute for Stem Cell and Regenerative Medicine, Seattle, WA (United States); Shan, Bin; Esteves, Kyle C. [Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA (United States); Lin, Zhen; Flemington, Erik K. [Department of Pathology, Tulane University School of Medicine, New Orleans, LA (United States); Lasky, Joseph A., E-mail: jlasky@tulane.edu [Department of Medicine, Section of Pulmonary Disease and Critical Care, Tulane University School of Medicine, New Orleans, LA (United States)

    2011-06-20

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

  6. Leukemia

    MedlinePLUS

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  7. Nuclear body movement is determined by chromatin accessibility and dynamics

    E-print Network

    Rippe, Karsten

    Nuclear body movement is determined by chromatin accessibility and dynamics Sabine M. Go¨ risch) Promyelocytic leukemia (PML) and Cajal bodies are mobile sub- nuclear organelles, which are involved in understanding their biological functions is their mobility. The diffusion properties of PML and Cajal bodies

  8. Telomerase-negative Immortalized Human Cells Contain a Novel Type of Promyelocytic Leukemia (PML) Body1

    Microsoft Academic Search

    Thomas R. Yeager; Axel A. Neumann; Anna Englezou; Lily I. Huschtscha; Jane R. Noble; Roger R. Reddel

    Telomerase-negative immortalized human cells maintain their tel- omeres by a mechanism known as alternative lengthening of telomeres (ALT). We report here that ALT cells contain a novel promyelocytic leukemia (PML) body (ALT-associated PML body, APB). APBs are large donut-shaped nuclear structures containing PML protein, telomeric DNA, and the telomere binding proteins human telomere repeat binding factors 1 and 2. Immunostaining

  9. Biophysical and Functional Analyses Suggest That Adenovirus E4-ORF3 Protein Requires Higher-order Multimerization to Function against Promyelocytic Leukemia Protein Nuclear Bodies*

    PubMed Central

    Patsalo, Vadim; Yondola, Mark A.; Luan, Bowu; Shoshani, Ilana; Kisker, Caroline; Green, David F.; Raleigh, Daniel P.; Hearing, Patrick

    2012-01-01

    The early region 4 open reading frame 3 protein (E4-ORF3; UniProt ID P04489) is the most highly conserved of all adenovirus-encoded gene products at the amino acid level. A conserved attribute of the E4-ORF3 proteins of different human adenoviruses is the ability to disrupt PML nuclear bodies from their normally punctate appearance into heterogeneous filamentous structures. This E4-ORF3 activity correlates with the inhibition of PML-mediated antiviral activity. The mechanism of E4-ORF3-mediated reorganization of PML nuclear bodies is unknown. Biophysical analysis of the purified WT E4-ORF3 protein revealed an ordered secondary/tertiary structure and the ability to form heterogeneous higher-order multimers in solution. Importantly, a nonfunctional E4-ORF3 mutant protein, L103A, forms a stable dimer with WT secondary structure content. Because the L103A mutant is incapable of PML reorganization, this result suggests that higher-order multimerization of E4-ORF3 may be required for the activity of the protein. In support of this hypothesis, we demonstrate that the E4-ORF3 L103A mutant protein acts as a dominant-negative effector when coexpressed with the WT E4-ORF3 in mammalian cells. It prevents WT E4-ORF3-mediated PML track formation presumably by binding to the WT protein and inhibiting the formation of higher-order multimers. In vitro protein binding studies support this conclusion as demonstrated by copurification of coexpressed WT and L103A proteins in Escherichia coli and coimmunoprecipitation of WT·L103A E4-ORF3 complexes in mammalian cells. These results provide new insight into the properties of the Ad E4-ORF3 protein and suggest that higher-order protein multimerization is essential for E4-ORF3 activity. PMID:22573317

  10. Leukemia among participants in military maneuvers at a nuclear bomb test

    Microsoft Academic Search

    G. G. Caldwell; D. B. Kelley; C. W. Heath

    1980-01-01

    To test the possibility of a casual relationship between leukemia and exposure to nuclear radiation, the frequency of leukemia in personnel observing the detonation of a nuclear device called ''Smoky'' during August 1957 was determined. Of some 3224 men who witnessed the detonation, nine cases of leukemia were observed. They included four cases of acute myelocytic leukemia, three of chronic

  11. Whole-genome screening identifies proteins localized to distinct nuclear bodies

    PubMed Central

    Fong, Ka-wing; Li, Yujing; Wang, Wenqi; Ma, Wenbin; Li, Kunpeng; Qi, Robert Z.; Liu, Dan; Songyang, Zhou

    2013-01-01

    The nucleus is a unique organelle that contains essential genetic materials in chromosome territories. The interchromatin space is composed of nuclear subcompartments, which are defined by several distinctive nuclear bodies believed to be factories of DNA or RNA processing and sites of transcriptional and/or posttranscriptional regulation. In this paper, we performed a genome-wide microscopy-based screening for proteins that form nuclear foci and characterized their localizations using markers of known nuclear bodies. In total, we identified 325 proteins localized to distinct nuclear bodies, including nucleoli (148), promyelocytic leukemia nuclear bodies (38), nuclear speckles (27), paraspeckles (24), Cajal bodies (17), Sam68 nuclear bodies (5), Polycomb bodies (2), and uncharacterized nuclear bodies (64). Functional validation revealed several proteins potentially involved in the assembly of Cajal bodies and paraspeckles. Together, these data establish the first atlas of human proteins in different nuclear bodies and provide key information for research on nuclear bodies. PMID:24127217

  12. Chronic myelogenous leukemia (CML)

    MedlinePLUS

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  13. Leukemia among participants in military maneuvers at a nuclear bomb test. [Plumbbob Project

    Microsoft Academic Search

    G. G. Caldwell; D. B. Kelley; C. W. Jr. Heath

    1980-01-01

    Preliminary studies indicate that nine cases of leukemia have occurred among 3224 men who participated in military maneuvers during the 1957 nuclear test explosion Smoky. This represents a significant increase over the expected incidence of 3.5 cases. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, and one each of hairy cell and acute lymphocytic leukemia.

  14. Leukemia

    MedlinePLUS

    ... A-Z > Leukemia: What Is Leukemia? In This Topic What Is Leukemia? Who Is at Risk? Symptoms ... for More Information National Institute on Aging Related Topics Life After Cancer Other Cancer Topics The information ...

  15. Leukemia

    MedlinePLUS

    ... FR. The acute leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, Pa: ... Brien S. The chronic leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, Pa: ...

  16. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    ClinicalTrials.gov

    2015-06-08

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  17. Nuclear body formation and PML body remodeling by the human cytomegalovirus protein UL35

    SciTech Connect

    Salsman, Jayme; Wang Xueqi; Frappier, Lori, E-mail: lori.frappier@utoronto.ca

    2011-06-05

    The human cytomegalovirus (HCMV) UL35 gene encodes two proteins, UL35 and UL35a. Expression of UL35 in transfected cells results in the formation of UL35 nuclear bodies that associate with promyelocytic leukemia (PML) protein. PML forms the basis for PML nuclear bodies that are important for suppressing viral lytic gene expression. Given the important relationship between PML and viral infection, we have further investigated the association of UL35 with PML bodies. We demonstrate that UL35 bodies form independently of PML and subsequently recruit PML, Sp100 and Daxx. In contrast, UL35a did not form bodies; however, it could bind UL35 and inhibit the formation of UL35 bodies. The HCMV tegument protein pp71 promoted the formation of UL35 bodies and the cytoplasmic localization of UL35a. Similarly, UL35a shifted pp71 to the cytoplasm. These results indicate that the interplay between UL35, UL35a and pp71 affects their subcellular localization and likely their functions throughout infection.

  18. Childhood Leukemia

    MedlinePLUS

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  19. Nuclear bodies: multifunctional companions of the genome

    PubMed Central

    Dundr, Miroslav

    2012-01-01

    It has become increasingly apparent that gene expression is regulated by the functional interplay between spatial genome organization and nuclear architecture. Within the nuclear environment a variety of distinct nuclear bodies exist. They are dynamic, self-organizing structures that do not assemble as pre-formed entities but rather emerge as a direct reflection of specific activities associated with gene expression and genome maintenance. Here I summarize recent findings on functions of some of the most prominent nuclear bodies, including the nucleolus, Cajal body, PML nuclear body, Polycomb group body and the 53BP1 nuclear body. The emerging view is that their organization is orchestrated by similar principles, and they function in fundamental cellular processes involved in homeostasis, differentiation, development and disease. PMID:22541757

  20. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  1. Leukemia

    NSDL National Science Digital Library

    Patient Education Institute

    This patient education program explains what leukemia is and reviews the causes, symptoms, diagnosis, and treatment options. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

  2. Leukemia among participants in military maneuvers at a nuclear bomb test. [Plumbbob Project

    SciTech Connect

    Caldwell, G.G.; Kelley, D.B.; Heath, C.W. Jr.

    1980-10-03

    Preliminary studies indicate that nine cases of leukemia have occurred among 3224 men who participated in military maneuvers during the 1957 nuclear test explosion Smoky. This represents a significant increase over the expected incidence of 3.5 cases. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, and one each of hairy cell and acute lymphocytic leukemia. At time of diagnosis, patient ages ranged from 21 to 60 years (mean, 41.8 years) and the interval from time of nuclear test to diagnosis from two to 19 years (mean, 14.2 years). Film-badge records, which are available for eight of the nine men, indicated gamma radiation exposure levels ranging from 0 to 2977 mrem (mean, 1033 mrem). Mean film-badge gamma dose for the entire Smoky cohort was 466.2 mrem.

  3. Acute Lymphoblastic Leukemia (ALL)

    MedlinePLUS

    ... this page Print this page Acute lymphoblastic leukemia (ALL) Acute lymphoblastic leukemia (ALL) is a fast-growing cancer of a type ... that your body needs. Tweet Acute Lymphoblastic Leukemia (ALL) How transplant can treat ALL Transplant outcomes for ...

  4. The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

    PubMed

    Holter-Chakrabarty, Jennifer L; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D; Artz, Andrew S; Baron, Frédéric; Bredeson, Christopher N; Dvorak, Christopher C; Epstein, Robert B; Lazarus, Hillard M; Olsson, Richard F; Selby, George B; Williams, Kirsten M; Cooke, Kenneth R; Pasquini, Marcelo C; McCarthy, Philip L

    2015-07-01

    Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning. PMID:25840335

  5. Coilin Methylation Regulates Nuclear Body Formation

    Microsoft Academic Search

    Michael D. Hebert; Karl B. Shpargel; Jason K. Ospina; Karen E. Tucker; A. Gregory Matera

    2002-01-01

    Cajal bodies (CBs) are nuclear suborganelles involved in biogenesis of small RNAs. Twin structures, called gems, contain high concentrations of the survival motor neurons (SMN) protein complex. CBs and gems often colocalize, and communication between these subdomains is mediated by coilin, the CB marker. Coilin contains symmetrical dimethylarginines that modulate its affinity for SMN, and, thus, localization of SMN complexes

  6. Fludarabine Nucleoside Modulates Nuclear “Survival and Death” Proteins in Resistant Chronic Lymphocytic Leukemia Cells

    Microsoft Academic Search

    Silke Henrich; Swetlana Mactier; Giles Best; Stephen P. Mulligan; Ben Crossett; Richard Ian Christopherson

    2011-01-01

    The nuclear mechanisms by which fludarabine nucleoside (F-ara-A) induces apoptosis have been investigated in human MEC1 cells derived from B-cell chronic lymphocytic leukemia. Upon treatment of cells with F-ara-A (100 ?M, 72 hours), 15 nuclear proteins changed in abundance by more than 2-fold. Nuclear proteins up-regulated included calmodulin (4.3-fold), prohibitin (3.9-fold), ?-actin variant (3.7-fold), and structure-specific recognition protein 1 (3.7-fold);

  7. Relativistic nuclear many-body theory

    SciTech Connect

    Serot, B.D. (Indiana Univ., Bloomington, IN (United States)); Walecka, J.D. (Southeastern Universities Research Association, Newport News, VA (United States). Continuous Electron Beam Accelerator Facility)

    1991-09-11

    Nonrelativistic models of nuclear systems have provided important insight into nuclear physics. In future experiments, nuclear systems will be examined under extreme conditions of density and temperature, and their response will be probed at momentum and energy transfers larger than the nucleon mass. It is therefore essential to develop reliable models that go beyond the traditional nonrelativistic many-body framework. General properties of physics, such as quantum mechanics, Lorentz covariance, and microscopic causality, motivate the use of quantum field theories to describe the interacting, relativistic, nuclear many-body system. Renormalizable models based on hadronic degrees of freedom (quantum hadrodynamics) are presented, and the assumptions underlying this framework are discussed. Some applications and successes of quantum hadrodynamics are described, with an emphasis on the new features arising from relativity. Examples include the nuclear equation of state, the shell model, nucleon-nucleus scattering, and the inclusion of zero-point vacuum corrections. Current issues and problems are also considered, such as the construction of improved approximations, the full role of the quantum vacuum, and the relationship between quantum hadrodynamics and quantum chromodynamics. We also speculate on future developments. 103 refs., 18 figs.

  8. Few-body models for nuclear astrophysics

    NASA Astrophysics Data System (ADS)

    Descouvemont, P.; Baye, D.; Suzuki, Y.; Aoyama, S.; Arai, K.

    2014-04-01

    We present applications of microscopic models to nuclear reactions of astrophysical interest, and we essentially focus on few-body systems. The calculation of radiative-capture and transfer cross sections is outlined, and we discuss the corresponding reaction rates. Microscopic theories are briefly presented, and we emphasize on the matrix elements of four-body systems. The microscopic extension of the R-matrix theory to nuclear reactions is described. Applications to the 2H(d, ?)4He, 2H(d, p)3H and 2H(d, n)3He reactions are presented. We show the importance of the tensor force to reproduce the low-energy behaviour of the cross sections.

  9. A Cluster of Childhood Leukemia near a Nuclear Reactor in Northern Germany

    Microsoft Academic Search

    Wolfgang Hoffmann; Helga Dieckmann; Hayo Dieckmann; Inge Schmitz-feuerhake

    1997-01-01

    Between February 1990 and December 1995, professionals diagnosed six cases of childhood leukemia among residents of the small rural community of Elbmarsch in Northern Germany. Five of these cases were diagnosed in only a 16-mo period between February 1990 and May 1991. All cases lived in close proximity (i.e., 500–4 500 m) to Germany's largest capacity nuclear boiling-water reactor. We

  10. Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies

    PubMed Central

    Salsman, Jayme; Zimmerman, Nicole; Chen, Tricia; Domagala, Megan; Frappier, Lori

    2008-01-01

    Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes. PMID:18617993

  11. Chronic Lymphocytic Leukemia

    MedlinePLUS

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  12. Chronic Myeloid Leukemia

    MedlinePLUS

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  13. Acute Myeloid Leukemia

    MedlinePLUS

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  14. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

    PubMed Central

    Atkinson, Helen C.; Marsh, Julie A.; Rath, Shoshana R.; Kotecha, Rishi S.; Gottardo, Nicholas G.; Cole, Catherine H.; Choong, Catherine S.

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  15. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    PubMed

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL. PMID:26101530

  16. Childhood Leukemia in the Vicinity of the Geesthacht Nuclear Establishments near Hamburg, Germany

    PubMed Central

    Hoffmann, Wolfgang; Terschueren, Claudia; Richardson, David B.

    2007-01-01

    Background During 1990–1991 a childhood leukemia cluster was observed in the sparsely populated region surrounding two nuclear establishments southeast of Hamburg, Germany. Since then, several new cases have been reported. Recently a possible accidental release of radionuclides in 1986 was hypothesized. Objective The objective of this study was to analyze the childhood leukemia incidence in this area since 1990. Methods All incident cases (< 15 years of age) were ascertained during 1990–2005 within a 5-km radius of the Krümmel nuclear power plant. We derived standardized incidence ratios (SIRs) using county and national leukemia incidence rates as referents. We stratified analyses by calendar period and attained age, and by subdividing the study region into areas north versus south of the Elbe river. Results Fourteen cases were ascertained in the study area, whereas 4.0 were expected based on national referent rates [1990–2005: SIR = 3.5; 95% confidence interval (CI), 1.9–5.9]. The excess was not confined to the early 1990s; for the more recent time period 1999–2005, the SIR is still elevated (SIR = 2.7; 95% CI, 0.9–6.2). SIRs of greatest magnitude were observed for children 0–4 years of age (SIR = 4.9; 95% CI, 2.4–9.0) and for residents south of the Elbe (SIR = 7.5; 95% CI, 2.8–16.4). Conclusions The incidence in this region is significantly higher than the childhood leukemia incidence for Germany as a whole. To date, no unique hazards have been identified in this population. The fact that the elevated rates have persisted in this community for > 15 years warrants further investigation. PMID:17589605

  17. A cluster of childhood leukemia near a nuclear reactor in northern Germany.

    PubMed

    Hoffmann, W; Dieckmann, H; Dieckmann, H; Schmitz-Feuerhake, I

    1997-01-01

    Between February 1990 and December 1995, professionals diagnosed six cases of childhood leukemia among residents of the small rural community of Elbmarsch in northern Germany. Five of these cases were diagnosed in only a 16-mo period between February 1990 and May 1991. All cases lived in close proximity (i.e., 500-4,500 m) to Germany's largest capacity nuclear boiling-water reactor. We calculated standardized incidence ratios and exact 95% confidence intervals for a 5-km-radius circular area around the plant. The standardized incidence ratio for the time period 1990-1995 was 460 (95% confidence interval: 210, 1,030). The analysis was restricted further to the years 1990 and 1991, and the standardized incidence ratio increased to 1,180 (95% confidence interval: 490, 2,830). Presently, this cluster of childhood leukemia cases cannot be explained in terms of established and putative risk factors--including radiation from medical sources--for childhood leukemia. PMID:9210727

  18. Hepatitis C-associated liver carcinogenesis: Role of PML nuclear bodies

    PubMed Central

    Herzer, Kerstin; Gerken, Guido; Hofmann, Thomas G

    2014-01-01

    Successful escape from immune response characterises chronic hepatitis C virus (HCV) infection, which results in persistence of infection in about 80% of the patients. The deleterious consequences are cirrhosis and hepatocellular carcinoma. HCV accounts the most frequent cause for hepatocellular carcinoma (HCC) and liver transplantation (LT) in the western world. The underlying molecular mechanisms how HCV promotes tumor development are largely unknown. There is some in vitro and in vivo evidence that HCV interferes with the tumor suppressor PML and may thereby importantly contribute to the HCV-associated pathogenesis with respect to the development of HCC. The tumor suppressor protein “promyelocytic leukemia” (PML) has been implicated in the regulation of important cellular processes like differentiation and apoptosis. In cancer biology, PML and its associated nuclear bodies (NBs) have initially attracted intense interest due to its role in the pathogenesis of acute promyelocytic leukemia (APL). More recently, loss of PML has been implicated in human cancers of various histologic origins. Moreover, number and intensity of PML-NBs increase in response to interferons (IFNs) and there is evidence that PML-NBs may represent preferential targets in viral infections. Thus, PML could not only play a role in the mechanisms of the antiviral action of IFNs but may also be involved in a direct oncogenic effect of the HCV on hepatocytes. This review aims to summarise current knowledge about HCV-related liver carcinogenesis and to discuss a potential role of the nuclear body protein PML for this this hard-to-treat cancer. PMID:25253937

  19. SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies

    SciTech Connect

    Haekli, Marika [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland); Karvonen, Ulla [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland); Jaenne, Olli A. [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland); Department of Clinical Chemistry, Helsinki University Central Hospital, FI-00014 Helsinki (Finland); Palvimo, Jorma J. [Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki (Finland) and Department of Medical Biochemistry, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio (Finland)]. E-mail: jorma.palvimo@helsinki.fi

    2005-03-10

    Small nuclear RING finger protein SNURF (RNF4) is involved in transcriptional and cell growth regulation. We show here that a significant portion of endogenous SNURF localizes to nuclear bodies (NBs) that overlap with or are adjacent to domains containing endogenous promyelocytic leukemia (PML) protein and small ubiquitin-like modifier-1 (SUMO-1). In biochemical assays, SNURF efficiently binds SUMO-1 in a noncovalent fashion. SNURF is also covalently modified by SUMO-1 at nonconsensus attachment sites. Ectopic expression of SUMO-1 markedly enhances the interaction between PML3 (PML IV) and SNURF, but covalent attachment of SUMO-1 to neither protein is required. Moreover, overexpression of PML3, but not PML-L (PML III), abolishes the coactivation function of SNURF in transactivation assays, which parallels the ability of PML3 to recruit SNURF to nuclear bodies. In sum, we have identified SNURF as a novel component in PML bodies and suggest that SUMO-1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of SNURF.

  20. Computational analysis of whole body CT documents a bone structure alteration in adult advanced chronic lymphocytic leukemia

    E-print Network

    Piana, Michele

    advanced chronic lymphocytic leukemia Manuscript Type: Original Research Advances in Knowledge: 1. Advanced chronic lymphocytic leukemia (ACLL) causes structural skeletal alterations, quantifiable by computational structure and bone marrow metabolism in adult patients with suspected advanced chronic lymphocytic leukemia

  1. The ND10 Component Promyelocytic Leukemia Protein Relocates to Human Papillomavirus Type 1 E4 Intranuclear Inclusion Bodies in Cultured Keratinocytes and in Warts

    PubMed Central

    Roberts, Sally; Hillman, Michele L.; Knight, Gillian L.; Gallimore, Phillip H.

    2003-01-01

    Human papillomavirus type 1 (HPV1) E4 protein is associated with cytoplasmic and nuclear inclusions in productively infected keratinocytes. Here we have used transient expression of HPV1 E4 (also known as E1^E4) protein in keratinocytes to reproduce formation of E4 inclusions. Immunofluorescence analysis showed that progressive formation of inclusions correlated with diminished colocalization between E4 and keratin intermediate filaments (IFs). Our results support a model in which the HPV1 E4-keratin IF association is transient, occurring only at an early stage of inclusion formation. We also demonstrate that E4 induces relocation of the promyelocytic leukemia protein (PML) from multiple intranuclear speckles (ND10 bodies) to the periphery of nuclear E4 inclusions and that this activity is specific to full-length E4 protein. Analysis of HPV1-induced warts demonstrated that nuclear PML-E4 inclusions were present in productively infected keratinocytes, indicating that reorganization of PML occurs during the virus's replication cycle. It has been suggested that ND10 bodies are the sites for papillomavirus genome replication and virion assembly. Our finding that E4 induces reorganization of ND10 bodies in vitro and in vivo is further strong evidence that these domains play an important role in the papillomavirus life cycle. This study indicates that HPV1 is analogous to other DNA viruses that disrupt or reorganize ND10 domains, possibly to increase efficiency of virus infection. We hypothesize that HPV1 E4-induced reorganization of PML is necessary for efficient replication of the virus during the virus-producing phase. PMID:12477870

  2. Chronic Myelogenous Leukemia (CML) (For Parents)

    MedlinePLUS

    ... Causes Signs and Symptoms Diagnosis Treatment Coping About Leukemia Leukemia is a type of cancer that affects the ... and protect the body against disease. But in leukemia, WBCs turn cancerous and multiply when they shouldn' ...

  3. Acute Myeloid Leukemia (AML) (For Parents)

    MedlinePLUS

    ... Causes Signs and Symptoms Diagnosis Treatment Coping About Leukemia Leukemia is a type of cancer that affects the ... and protect the body against disease. But in leukemia, WBCs turn cancerous and multiply when they shouldn' ...

  4. Time-lapse imaging of nuclear bodies.

    PubMed

    Hutten, Saskia; Swift, Samuel; Lamond, Angus I

    2015-01-01

    Fluorescence microscopy is a powerful technique that has become central in the study of the structure and function of biological specimens. This is due in large part to its specificity and versatility. Although an understanding of structure-typically through high-resolution imaging of fixed material-has proved an important tool to understanding function, fluorescence microscopy also offers a mechanism to interrogate cells in the living state, providing a means to explore dynamic process within the specimen over long time periods at high temporal resolution. The cell nucleus is a highly compartmented environment whose components are often highly motile and in a constant state of flux. The ability to monitor the dynamic behavior of nuclear bodies by live-cell imaging provides the researcher with important information regarding underlying mechanistic processes relating to their formation and maintenance. Two techniques have proved particularly valuable to our study of cellular dynamics and molecular mobility, namely, time-lapse imaging and fluorescence recovery after photobleaching (FRAP). Time-lapse microscopy allows for qualitative and quantitative analysis of a wide range of events at the cellular and subcellular level. FRAP provides a mechanism to study the mobility of a population of proteins in a range of conditions within discrete areas of the biological specimen. Therefore, fluorescence microscopy is unique in its ability to provide data at high temporal resolution and in such exquisite detail. PMID:25555575

  5. Body language: the function of PML nuclear bodies in apoptosis regulation

    Microsoft Academic Search

    T G Hofmann; H Will

    2003-01-01

    Promyelocytic leukaemia (PML) nuclear bodies (NBs) are macromolecular nuclear domains present in virtually every mammalian cell. PML nuclear bodies (PML-NBs) were functionally linked to various fundamental cellular processes, including transcriptional control, tumour suppression and apoptosis regulation. Supporting the important function of PML and its associated NBs in apoptosis regulation, several apoptotic regulators localise to PML-NBs, and cells from PML-deficient mice

  6. Regulation of Neuronal Differentiation by Proteins Associated with Nuclear Bodies

    PubMed Central

    Förthmann, Benjamin; van Bergeijk, Jeroen; Lee, Yu-Wei; Lübben, Verena; Schill, Yvonne; Brinkmann, Hella; Ratzka, Andreas; Stachowiak, Michal K.; Hebert, Michael; Grothe, Claudia; Claus, Peter

    2013-01-01

    Nuclear bodies are large sub-nuclear structures composed of RNA and protein molecules. The Survival of Motor Neuron (SMN) protein localizes to Cajal bodies (CBs) and nuclear gems. Diminished cellular concentration of SMN is associated with the neurodegenerative disease Spinal Muscular Atrophy (SMA). How nuclear body architecture and its structural components influence neuronal differentiation remains elusive. In this study, we analyzed the effects of SMN and two of its interaction partners in cellular models of neuronal differentiation. The nuclear 23 kDa isoform of Fibroblast Growth Factor – 2 (FGF-223) is one of these interacting proteins – and was previously observed to influence nuclear bodies by destabilizing nuclear gems and mobilizing SMN from Cajal bodies (CBs). Here we demonstrate that FGF-223 blocks SMN-promoted neurite outgrowth, and also show that SMN disrupts FGF-223-dependent transcription. Our results indicate that FGF-223 and SMN form an inactive complex that interferes with neuronal differentiation by mutually antagonizing nuclear functions. Coilin is another nuclear SMN binding partner and a marker protein for Cajal bodies (CBs). In addition, coilin is essential for CB function in maturation of small nuclear ribonucleoprotein particles (snRNPs). The role of coilin outside of Cajal bodies and its putative impacts in tissue differentiation are poorly defined. The present study shows that protein levels of nucleoplasmic coilin outside of CBs decrease during neuronal differentiation. Overexpression of coilin has an inhibitory effect on neurite outgrowth. Furthermore, we find that nucleoplasmic coilin inhibits neurite outgrowth independent of SMN binding revealing a new function for coilin in neuronal differentiation. PMID:24358231

  7. MRI Morphometry of Mamillary Bodies, Caudate Nuclei, and Prefrontal Cortices After Chemotherapy for Childhood Leukemia: Multivariate Models of Early and Late Developing Memory Subsystems

    Microsoft Academic Search

    Kristina T. Ciesielski; Paul G. Lesnik; Edward C. Benzel; Blaine L. Hart; John A. Sanders

    1999-01-01

    Neurotoxic intrathecal chemotherapy for childhood acute lymphoblastic leukemia (ALL) affects developing structures and functions of memory and learning subsystems selectively. Results show significant reductions in magnetic resonance imaging morphometry of mamillary bodies, components of the corticolimbic–diencephalic subsystem subserving functionally later developing, single-trial memory, nonsignificant changes in bilateral heads of the caudate nuclei, components of the corticostriatal subsystem subserving functionally earlier

  8. Stages of Hairy Cell Leukemia

    MedlinePLUS

    ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Research NCI’s Role in Cancer ... Search Home Cancer Types Leukemia Patient Leukemia Patient Adult ALL Treatment Adult AML Treatment CLL Treatment CML ...

  9. Computational Nuclear Quantum Many-Body Problem: The UNEDF Project

    E-print Network

    Scott Bogner; Aurel Bulgac; Joseph A. Carlson; Jonathan Engel; George Fann; Richard J. Furnstahl; Stefano Gandolfi; Gaute Hagen; Mihai Horoi; Calvin W. Johnson; Markus Kortelainen; Ewing Lusk; Pieter Maris; Hai Ah Nam; Petr Navratil; Witold Nazarewicz; Esmond G. Ng; Gustavo P. A. Nobre; Erich Ormand; Thomas Papenbrock; Junchen Pei; Steven C. Pieper; Sofia Quaglioni; Kenneth J. Roche; Jason Sarich; Nicolas Schunck; Masha Sosonkina; Jun Terasaki; Ian J. Thompson; James P. Vary; Stefan M. Wild

    2013-04-12

    The UNEDF project was a large-scale collaborative effort that applied high-performance computing to the nuclear quantum many-body problem. UNEDF demonstrated that close associations among nuclear physicists, mathematicians, and computer scientists can lead to novel physics outcomes built on algorithmic innovations and computational developments. This review showcases a wide range of UNEDF science results to illustrate this interplay.

  10. Detection by monoclonal antibodies of the Wilms' tumor (WT1) nuclear protein in patients with acute leukemia.

    PubMed

    Menssen, H D; Renkl, H J; Rodeck, U; Kari, C; Schwartz, S; Thiel, E

    1997-03-01

    The WT1 gene encodes a transcriptional regulator which during embryogenesis is involved in growth control and differentiation of diverse tissues. It is also expressed in few human malignancies, including acute leukemia. We tested 3 different monoclonal antibodies (MAbs H2, H7, HCl7) and the polyvalent serum WTC-19 for WT1 protein detection in mononuclear cell (MNC) preparations of 104 newly diagnosed acute leukemia patients. Using RT-PCR, these MNC preparations were also analyzed for WT1 gene expression. MAbs H2, H7 and HCl7 and the polyclonal WTC-19 exhibited nuclear immunoreactivity in 63 of 99, 28 of 56, 38 of 60 and 22 of 43 WT1 gene-expressing leukemia samples, respectively. With these antibodies, no WT1 immunoreactivity was found in MNCs from blood of healthy volunteers, from CD34+ progenitor cell-enriched leukapheresis products of patients conditioned for peripheral stem cell harvest or from reactive bone marrow. Contrary to WTC-19, all MAbs reacted highly specifically with the WT1 protein (0.71 vs. 1.0). The WT1 protein was heterogeneously detected in leukemia blast preparations by all antibodies, irrespective of cell morphology. Very few HL60 cells and blasts from newly diagnosed leukemia patients interspersed among normal blood MNCs (50 blasts among 5 x 10(5) MNCs) were easy to identify by indirect immunofluorescence using MAbs H2 and HCl7. Taken together, MAbs H2 and HCl7 were superior to MAb H7 and the polyvalent WTC-19 in detecting the WT1 nuclear protein. PMID:9052749

  11. Hans Bethe: The Nuclear Many Body Problem

    E-print Network

    Jeremy Holt; Gerald Brown

    2005-09-07

    We discuss the work of Hans Bethe and others in formulating a theoretical foundation for the nuclear shell model. Written for a general audience, this article describes the evolution from Brueckner's reaction matrix theory to the Moszkowski-Scott separation method and ultimately to the Reference Spectrum method of Bethe, Brandow, and Petschek. We also discuss connections with the recently developed low momentum nucleon-nucleon interactions.

  12. Total body irradiation plus cyclophosphamide versus busulphan with cyclophosphamide as conditioning regimen for patients with leukemia undergoing allogeneic stem cell transplantation: a meta-analysis.

    PubMed

    Shi-Xia, Xu; Xian-Hua, Tang; Hai-Qin, Xu; Bo, Feng; Xiang-Feng, Tang

    2010-01-01

    The aim of the study was to compare the therapeutic efficacy of total body irradiation (TBI)/cyclophosphamide (CY) versus BU/CY as conditioning regimen for leukemia. We electronically searched the Cochrane Central Register of Controlled Trials, Medline, Embase, CIBMTR and critically appraised all relevant articles (1990.01-2009.04). Comparative studies were evaluated on clinical therapeutic effects of TBI/CY and busulphan BU/CY regimens with assessement of engraftment, relapse, complications, and disease-free survival (DFS). Eighteen trials totaling 3172 patients have been assessed. Pooled comparisons of studies indicated that for patients with acute leukemia (ALL and AML), the TBI/CY regimen lead to lower rates of leukemia relapse, lower transplant-related mortality (TRM), and higher DFS, while for chronic myeloid leukemia (CML), the TBI/CY regimen had a higher rate of leukemia relapse, lower TRM, and similar DFS. The TBI/CY regimen was associated with similar occurrence of engraftment, acute and chronic graft-versus-host disease (GVHD), but with higher rates of cataract [odds ratio (OR) 12.69, p = 0.01], interstitial pneumonitis, later growth or development problems [OR 5.04, p = 0.008]. BU/CY regimen was associated with higher rates of complications like liver veno-occlusive disease [OR 0.43, p < 0.00001], hemorrhagic cystitis, and TRM. Our meta-analysis confirmed that different regimens and type of leukemia may affect the complications and outcome. An analysis of the effects of other regimens need to be carried out by large sample and well-designed clinical trials. PMID:20055658

  13. Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

    PubMed Central

    Navascues, Joaquin; Berciano, Maria T.; Tucker, Karen E.

    2006-01-01

    Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body. PMID:15164213

  14. Few-Body Nuclear Wave Functions

    NASA Astrophysics Data System (ADS)

    Chaudhary, Irfan; Hagelstein, Peter L.

    2005-12-01

    This is where the abstract should be placed. It should consist of one paragraph and give a concise summary of the material in the article below. Replace the title, authors, and addresses within the curly brackets with your own title, authors, and addresses. You may have as many authors and addresses as you wish. It's preferable not to use footnotes in the abstract or the title; the acknowledgments for funding bodies etc. are placed in a separate section at the end of the text.

  15. Nuclear matter equation of state and three-body forces

    SciTech Connect

    Mansour, H. M. M.; Algamoudi, A. M. A. [Cairo University, Physics Department, Faculty of Science (Egypt)

    2012-04-15

    The energy per particle, symmetry energy, pressure, and free energy are calculated for symmetric nuclear matter using BHF approach with modern nucleon-nucleon CD-Bonn, Nijm1, Argonne v{sub 18}, and Reid 93 potentials. To obtain saturation in nuclear matter we add three-body interaction terms which are equivalent to a density-dependent two-nucleon interaction a la Skyrme force. Good agreement is obtained in comparison with previous theoretical estimates and experimental data.

  16. Whole-Body Sleeping Beauty Mutagenesis Can Cause Penetrant Leukemia\\/Lymphoma and Rare High-Grade Glioma without Associated Embryonic Lethality

    Microsoft Academic Search

    Lara S. Collier; David J. Adams; Christopher S. Hackett; Laura E. Bendzick; Keiko Akagi; Michael N. Davies; Miechaleen D. Diers; Fausto J. Rodriguez; Aaron M. Bender; Christina Tieu; Ilze Matise; Adam J. Dupuy; Neal G. Copeland; Nancy A. Jenkins; J. Graeme Hodgson; William A. Weiss; Robert B. Jenkins; David A. Largaespada

    2009-01-01

    The Sleeping Beauty (SB) transposon system has been used as a somatic mutagen to identify candidate cancer genes. In previous studies, efficient leukemia\\/lymphoma formation on an otherwise wild-type genetic background occurred in mice undergoing whole-body mobilization of transposons, but was accompanied by high levels of embryonic lethality. To explore the utility of SB for large-scale cancer gene dis- covery projects,

  17. HPV16 E7 Reveals a Link between DNA Replication Stress, Fanconi Anemia D2 Protein, and Alternative Lengthening of Telomere-Associated Promyelocytic Leukemia Bodies

    Microsoft Academic Search

    Nicole Spardy; Anette Duensing; Elizabeth E. Hoskins; Susanne I. Wells; Stefan Duensing

    2008-01-01

    Expression of the high-risk human papillomavirus (HPV-16) E7 oncoprotein extends the life span of primary human keratinocytes and partially restores telomere length in the absence of telomerase. The molecular basis of this activity is incompletely understood. Here, we show that HPV-16 E7 induces an increased formation of alternative lengthening of telomeres (ALT)-associated promyelocytic leukemia bodies (APBs) in early passage primary

  18. Nuclear Many-Body Physics Where Structure And Reactions Meet

    E-print Network

    Naureen Ahsan; Alexander Volya

    2009-06-24

    The path from understanding a simple reaction problem of scattering or tunneling to contemplating the quantum nuclear many-body system, where structure and continuum of reaction-states meet, overlap and coexist, is a complex and nontrivial one. In this presentation we discuss some of the intriguing aspects of this route.

  19. Relationship between leukemia incidence and residing and/or working near the Pilgrim 1 nuclear power plant in Plymouth, Massachusetts

    SciTech Connect

    Morris, M.S.

    1992-01-01

    To determine whether a strong association between leukemia incidence between 1978 and 1986 and potential for exposure to radiation emitted from the Pilgrim 1 nuclear power plant in Plymouth, Massachusetts was a spurious finding resulting from either (1) failure to account for temporal variation in the level of radioactivity released from the plant or (2) inattention to certain potentially confounding factors, additional age/sex-matched case-control analyses controlled for the effects of socioeconomic status (SES), work history, and cigarette smoking were performed with data collected in the Southeastern Massachusetts Health Investigation -- a study of leukemia among residents aged 13 and older of 22 southeastern Massachusetts towns. None of the additional analyses, including incorporation of emissions data into the exposure-assessment scheme and crude attempts to control for (1) medical-radiation exposure, (2) potential for exposure to pesticides sprayed on cranberry bogs, or (3) workplace exposure to radiation, chemical solvents, dust, or fumes, altered the finding of a statistically significant dose-response relationship between leukemia incidence and potential for exposure to radioactive emissions. The trend in the association over time was not entirely consistent, however, with the hypothesis that unusually large amounts of radioactivity reportedly released from the plant during the mid-1970s were responsible for the observed effects. Recommendations were made for further study of the Plymouth-area population for studies of this problem elsewhere.

  20. Aberrant nuclear factor-kappa B activity in acute myeloid Leukemia: from molecular pathogenesis to therapeutic target

    PubMed Central

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-01-01

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-?B) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-?B has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-?B signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-?B signaling transduction including canonical and non-canonical NF-?B pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-?B activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade®), which is a NF-?B inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-?B inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  1. Thermodynamic properties of nuclear matter with three-body forces

    SciTech Connect

    Soma, V. [Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland); Bozek, P. [Institute of Physics, Rzeszow University, PL-35-959 Rzeszow (Poland); Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland)

    2009-08-15

    We calculate thermodynamic quantities in symmetric nuclear matter within the self-consistent Green's functions method including three-body forces. The thermodynamic potential is computed directly from a diagrammatic expansion, implemented with the CD-Bonn and Nijmegen nucleon-nucleon potentials and the Urbana three-body forces. We present results for entropy and pressure up to temperatures of 20 MeV and densities of 0.32 fm{sup -3}. While the pressure is sensitive to the inclusion of three-body forces, the entropy is not. The unstable spinodal region is identified and the critical temperature associated to the liquid-gas phase transition is determined. When three-body forces are added we find a strong reduction of the critical temperature, obtaining T{sub c}{approx_equal}12 MeV.

  2. Does Total Body Irradiation Conditioning Improve Outcomes of Myeloablative HLA-Identical Sibling Transplants for Chronic Lymphocytic Leukemia?

    PubMed Central

    Sabloff, Mitchell; Sobecks, Ronald M.; Ahn, Kwang Woo; Zhu, Xiaochun; de Lima, Marcos; Brown, Jennifer R.; Inamoto, Yoshihiro; Holland, H. Kent; Aljurf, Mahmoud D.; Laughlin, Mary J.; Kamble, Rammurti T.; Hsu, Jack W.; Wirk, Baldeep M.; Seftel, Matthew; Lewis, Ian D.; Arora, Mukta; Alyea, Edwin P.; Kalaycio, Matt E.; Cortes, Jorge; Maziarz, Richard T.; Gale, Robert Peter; Saber, Wael

    2014-01-01

    An allogeneic hematopoietic cell transplant (HCT) from an HLA-identical donor after high-dose (myeloablative) pre-transplant conditioning, is an effective therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a highly radiosensitive cancer, we hypothesized total body irradiation (TBI) conditioning regimens may be associated with better outcomes than those without TBI. To answer this we analyzed data from 180 subjects with CLL receiving myeloablative doses of TBI (N=126) or not (N=54), transplanted from an HLA-identical sibling donor, between 1995 and 2007 and reported to the Center for International Blood & Marrow Transplant Research (CIBMTR). At 5 years, treatment-related mortality was 48% (95% CI, 39–57%) vs. 50% (95% CI, 36–64%); p=NS. Relapse rates were 17% (95% CI, 11–25%) vs. 22% (95% CI, 11–35%); p=NS. Five-year progression-free survival and overall survival was 34% (95% CI, 26–43%) vs. 28% (95% CI, 15–42%); p=NS and 42% (95% CI, 33–51%) vs. 33% (95% CI, 19–48%); p=NS, respectively. The single most common cause of death in both cohorts was recurrent/progressive CLL. No variable tested in the multivariate analysis was found to significantly affect these outcomes including having failed fludarabine. Within the limitations of this study we found no difference in HLA-identical sibling transplant outcomes between myeloablative TBI and chemotherapy pre-transplant conditioning in persons with CLL. PMID:24321745

  3. Leukemia -- Eosinophilic

    MedlinePLUS

    ... are here Home > Types of Cancer > Leukemia - Eosinophilic Leukemia - Eosinophilic This is Cancer.Net’s Guide to Leukemia - Eosinophilic. Use the menu below to choose the Overview section to get started. ...

  4. Leukemia in the proximity of a German boiling-water nuclear reactor: evidence of population exposure by chromosome studies and environmental radioactivity.

    PubMed

    Schmitz-Feuerhake, I; Dannheim, B; Heimers, A; Oberheitmann, B; Schröder, H; Ziggel, H

    1997-12-01

    Exceptional elevation of children's leukemia appearing 5 years after the 1983 startup of the Krümmel nuclear power plant, accompanied by a significant increase of adult leukemia cases, led to investigations of radiation exposures of the population living near the plant. The rate of dicentric chromosomes in peripheral lymphocytes of seven parents of children with leukemia and in 14 other inhabitants near the plant was significantly elevated and indicated ongoing exposures over the years of its operation. These findings led to the hypothesis that chronic reactor leakages had occurred. This assumption is support by identification of artificial radioactivity in air, rainwater, soil and vegetation by the environmental monitoring program at the nuclear power plant. Calculations of the corresponding source terms show that emissions must have been well above authorized annual limits. Bone marrow doses supposedly result primarily through incorporation of bone-seeking beta- and alpha-emitters. PMID:9467072

  5. Critical nuclear charge of quantum mechanical three-body problem

    NASA Astrophysics Data System (ADS)

    Moini, Amirreza

    The critical nuclear charge Zc for a three-body quantum mechanical system consisting of positive and negative charges is the minimum charge for the system to remain in a bound state. This work presents a study of the critical nuclear charge for heliumlike systems with infinite nuclear mass, and also a range of the reduced mass up to 0.5. The results help us to resolve a discrepancy in the literature for the infinite mass case, and they are the first to study the dependence on reduced mass. It is found that Zc has a maximum at mM = 3525, which is intermediate between the atomic structure of helium, and the molecular structure of H+2 . Zc for the infinite mass case is found to be 0.911028267. This value is compatible with the result of Baker, et al, who found the upper bound for Zc to be 0.91103. However, it does not agree with other results in the literature. The understanding of the critical charge will bring us a deeper appreciation of the stability of a three-body system as a function of the reduced mass, correlation effects of coulombic potential and more importantly, the physics of a three-body quantum mechanical system.

  6. General Information about Chronic Myelogenous Leukemia

    MedlinePLUS

    ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Research NCI’s Role in Cancer ... Search Home Cancer Types Leukemia Patient Leukemia Patient Adult ALL Treatment Adult AML Treatment CLL Treatment CML ...

  7. General Information about Hairy Cell Leukemia

    MedlinePLUS

    ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Research NCI’s Role in Cancer ... Search Home Cancer Types Leukemia Patient Leukemia Patient Adult ALL Treatment Adult AML Treatment CLL Treatment CML ...

  8. General Information about Chronic Lymphocytic Leukemia

    MedlinePLUS

    ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Research NCI’s Role in Cancer ... Search Home Cancer Types Leukemia Patient Leukemia Patient Adult ALL Treatment Adult AML Treatment CLL Treatment CML ...

  9. Treatment Option Overview (Chronic Myelogenous Leukemia)

    MedlinePLUS

    ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Research NCI’s Role in Cancer ... Search Home Cancer Types Leukemia Patient Leukemia Patient Adult ALL Treatment Adult AML Treatment CLL Treatment CML ...

  10. PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals

    PubMed Central

    2014-01-01

    Background Promyelocytic leukemia nuclear bodies (PML-NBs) have been depicted as structures which are involved in processing cell damages and DNA double-strand break repairs. The study was designed to evaluate differences in patients’ PML-NBs response to stress factors like a cancerous disease and ionizing radiation exposure dependent on age. Methods In order to clarify the role of PML-NBs in the aging process, we examined peripheral blood monocytes of 134 cancer patients and 41 healthy individuals between 22 and 92 years of age, both before and after in vitro irradiation. Additionally, we analyzed the samples of the cancer patients after in vivo irradiation. Cells were immunostained and about 1600 cells per individual were analyzed for the presence of PML- and ?H2AX foci. Results The number of existing PML-NBs per nucleus declined with age, while the number of ?H2AX foci increased with age. There was a non-significant trend that in vivo irradiation increased the number of PML-NBs in cells of young study participants, while in older individuals PML-NBs tended to decrease. It can be assumed that PML-NBs decrease in number during the process of aging. Conclusion The findings suggest that there is a dysfunctional PML-NBs stress response in aged cells. PMID:24694011

  11. Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins

    PubMed Central

    Sahin, Umut; Ferhi, Omar; Jeanne, Marion; Benhenda, Shirine; Berthier, Caroline; Jollivet, Florence; Niwa-Kawakita, Michiko; Faklaris, Orestis; Setterblad, Niclas; Lallemand-Breitenbach, Valérie

    2014-01-01

    The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO–SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss. PMID:24637324

  12. Oxidative stress-induced assembly of PML nuclear bodies controls sumoylation of partner proteins.

    PubMed

    Sahin, Umut; Ferhi, Omar; Jeanne, Marion; Benhenda, Shirine; Berthier, Caroline; Jollivet, Florence; Niwa-Kawakita, Michiko; Faklaris, Orestis; Setterblad, Niclas; de Thé, Hugues; Lallemand-Breitenbach, Valérie

    2014-03-17

    The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO-SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss. PMID:24637324

  13. Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia

    PubMed Central

    Lapalombella, Rosa; Sun, Qingxiang; Williams, Katie; Tangeman, Larissa; Jha, Shruti; Zhong, Yiming; Goettl, Virginia; Mahoney, Emilia; Berglund, Caroline; Gupta, Sneha; Farmer, Alicia; Mani, Rajeswaran; Johnson, Amy J.; Lucas, David; Mo, Xiaokui; Daelemans, Dirk; Sandanayaka, Vincent; Shechter, Sharon; McCauley, Dilara; Shacham, Sharon; Kauffman, Michael

    2012-01-01

    The nuclear export protein XPO1 is overexpressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby inhibiting nuclear export of cargo proteins. The clinical relevance of SINEs was explored in chronic lymphocytic leukemia (CLL), a disease associated with recurrent XPO1 mutations. Evidence is presented that SINEs can restore normal regulation to the majority of the dysregulated pathways in CLL both in vitro and in vivo and induce apoptosis of CLL cells with a favorable therapeutic index, with enhanced killing of genomically high-risk CLL cells that are typically unresponsive to traditional therapies. More importantly, SINE slows disease progression, and improves overall survival in the E?-TCL1-SCID mouse model of CLL with minimal weight loss or other toxicities. Together, these findings demonstrate that XPO1 is a valid target in CLL with minimal effects on normal cells and provide a basis for the development of SINEs in CLL and related hematologic malignancies. PMID:23034282

  14. Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

    PubMed

    Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

    2014-02-01

    Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-? (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies. PMID:24412926

  15. Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias.

    PubMed

    Menssen, H D; Renkl, H J; Rodeck, U; Maurer, J; Notter, M; Schwartz, S; Reinhardt, R; Thiel, E

    1995-06-01

    The wt1 gene is located on chromosome 11p13 and encodes a zinc finger motif-containing transcription factor involved in regulation of growth and differentiation. Its expression was shown during embryonic development in various tissues as well as in a few human malignancies including acute leukemias. Using RT-PCR, we found wt1 gene expression in blast cells of the majority of 150 acute leukemia patients. Particularly, the wt1 transcript was detected in 12 of 14 (86%) pre-pre-B-ALL patients, in 33 of 41 (80%) cALL patients, in 23 of 31 (74%) T-ALL patients, and in 53 of 57 (93%) AML patients. Additionally, mononuclear cells from CML patients expressed the wt1 gene only when diagnosed with blast crisis. In contrast to acute human leukemias, mononuclear cells from reactive bone marrow (n = 4), and peripheral blood of healthy volunteers (n = 20), as well as normal peripheral CD34+ hematopoietic progenitors (n = 6) did not express the wt1 gene at detectable levels. Using the anti-WT1 MoAb 6F-H2 in an immunofluorescence assay on single cell level, we found the translated WT1 protein only in nuclei of leukemia blast cells but not in nuclei of normal CD34+ hematopoietic progenitor cells. Blast cells of 12 of 20 leukemia patients (60%) all tested positive for the wt1 gene expression by RT-PCR displayed a strong nuclear immunofluorescence. Its expression in the majority of human acute leukemias but not in normal mononuclear blood cells and normal CD34+ hematopoietic progenitors qualifies the wt1 gene transcript as a 'pan-acute leukemic' marker probably useful in monitoring minimal residual disease after chemotherapy and in detecting leukemic blast cells in purged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation. PMID:7596170

  16. Congenital leukemia.

    PubMed

    Raj, Aishwarya; Talukdar, Sewali; Das, Smita; Gogoi, Pabitra Kumar; Das, Damodar; Bhattacharya, Jina

    2014-09-01

    Congenital leukemia is a rare but a well-documented disease in which leukemic process is detected at birth or very shortly thereafter (Philip McCoy and Roy Overton, Commun Clin Cytom 22:85-88, 1995). These leukemias represent approximately 0.8 % of all childhood leukemias. We present a case of congenital acute myeloid leukemia manifesting from the very first day of birth. Diagnosis of acute myeloid leukemia was suspected by the presence of blasts in the peripheral blood smear and was confirmed on bone marrow by flowcytometry. Karyotyping revealed Trisomy 21. PMID:25332567

  17. Cell cycle-dependent alteration in NAC1 nuclear body dynamics and morphology

    NASA Astrophysics Data System (ADS)

    Wu, Pei-Hsun; Hung, Shen-Hsiu; Ren, Tina; Shih, Ie-Ming; Tseng, Yiider

    2011-02-01

    NAC1, a BTB/POZ family member, has been suggested to participate in maintaining the stemness of embryonic stem cells and has been implicated in the pathogenesis of human cancer. In ovarian cancer, NAC1 upregulation is associated with disease aggressiveness and with the development of chemoresistance. Like other BTB/POZ proteins, NAC1 forms discrete nuclear bodies in non-dividing cells. To investigate the biological role of NAC1 nuclear bodies, we characterized the expression dynamics of NAC1 nuclear bodies during different phases of the cell cycle. Fluorescence recovery after photobleaching assays revealed that NAC1 was rapidly exchanged between the nucleoplasm and NAC1 nuclear bodies in interphase cells. The number of NAC1 bodies significantly increased and their size decreased in the S phase as compared to the G0/G1 and G2 phases. NAC1 nuclear bodies disappeared and NAC1 became diffuse during mitosis. NAC1 nuclear bodies reappeared immediately after completion of mitosis. These results indicate that a cell cycle-dependent regulatory mechanism controls NAC1 body formation in the nucleus and suggest that NAC1 body dynamics are associated with mitosis or cytokinesis.

  18. [Comparison of total body irradiation-cyclophosphamide versus busulphan-cyclophosphamide as conditioning regimens for myelogenous leukemia: a meta-analysis].

    PubMed

    Xu, Shi-Xia; Tang, Xian-Hua; Chen, Hai-Qing; Feng, Bo; Xu, Hai-Qin; Chen, Xiao-Pei; Tang, Xiang-Feng

    2008-12-01

    Total body irradiation combined with cyclophosphamide (TBI/CY) and busulphan combined with cyclophosphamide (BU/CY) are standard conditioning regimens in hematological stem cell transplantation for patients with myelogenous leukemia. This study was aimed to compare the therapeutic efficacy of TBI/CY and BU/CY as conditioning regiment for acute or chronic myelogenous leukemia. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CNKI, CBM (Chinese Bio-medicine Database) had been searched for all relevant articles (1999-2007). Comparative studies were carried out on clinical therapeutic effects of TBI/CY and BU/CY including stem cell engraftment, relapse, complications, transplant-related mortality, and disease-free survival. A meta-analysis was performed using Review Manager 4.2 software and funnel plot regression was adopted to assess the publication bias. The results indicated that 2149 articles in English and 46 articles in Chinese were got, and finally 9 clinical trials with total 3039 patients have been assessed. No significantly difference was found in engraftment failure and transplant-related mortality resulting from TBI/CY and BU/CY conditioning regimens, but the incidence of veno-occlusion of liver and hemorrhagic cystitis obviously increased in BU/CY group after transplantation, the acute GVHD, interstitial pneumonia and cataract significantly increased in TBI/CY group. The relapse rate of AML in TBI/CY group was lower than that in BU/CY group, and the rate of long-term disease-free survival of AML patients in TBI/CY group also significantly lower than that in BU/CY group, but the relapse rate of CML in TBI/CY group after transplantation was obviously higher than that in BU/CY group, but there was no difference in longterm disease-free survival rate between the two conditioning regimens mentioned above. It is concluded that the meta-analysis confirms different effects of TBI/CY and BU/CY regimens on myelogenous leukemia transplantation. This result is useful for physicians to select treatment regimens. PMID:19099643

  19. Stages of Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

    MedlinePLUS

    ... Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Research NCI’s Role in Cancer ... Search Home Cancer Types Leukemia Patient Leukemia Patient Adult ALL Treatment Adult AML Treatment CLL Treatment CML ...

  20. Nuclear Bodies: Random Aggregates of Sticky Proteins or Crucibles of Macromolecular Assembly?

    PubMed Central

    Matera, A. Gregory; Izaguire-Sierra, Mario; Praveen, Kavita; Rajendra, T.K.

    2011-01-01

    The principles of self-assembly and self-organization are major tenets of molecular and cellular biology. Governed by these principles, the eukaryotic nucleus is composed of numerous subdomains and compartments, collectively described as nuclear bodies. Emerging evidence reveals that associations within and between various nuclear bodies and genomic loci are dynamic and can change in response to cellular signals. This review will discuss recent progress in our understanding of how nuclear body components come together, what happens when they form, and what benefit these subcellular structures may provide to the tissues or organisms in which they are found. PMID:19922869

  1. Total body irradiation as preparation for bone marrow transplantation in treatment of acute leukemia and aplastic anemia

    SciTech Connect

    Serota, F.T.; Burkey, E.D.; August, C.S.; D'Angio, G.J.

    1983-12-01

    In an attempt to improve survival while minimizing toxicity, many bone marrow transplant centers are now studying the use of cytoreduction regimens with an increased amount of radiation in single-dose or fractionated-exposure schedules for patients with leukemia and aplastic anemia. In order to review the current results, the literature prior to September, 1982 was surveyed and data were tabulated for each transplant center regarding the number of patients receiving transplants, diagnoses, cytoreduction regimen, clinical status, remission duration, relapse rate, causes of death and incidence of interstitial pneumonia. The incidence and severity of cataracts, growth failure, hypothyroidism and second malignant neoplasms were noted, and the data obtained from the literature search were updated and expanded by telephone questionnaire when possible. Marked variation in the technique of tranplantation was found among the participating institutions, making it difficult to determine the contribution of the various TBI doses, dose rates and fractionation schedules to the efficacy and toxicity of the combined regimen. In order to define the risk-benefit ratio of the various TBI regimens more clearly, prospective controlled, randomized studies will be required.

  2. [Chronic leukemia].

    PubMed

    Shibata, A; Narita, M

    1989-05-01

    As compared with advances in the treatment of acute leukemia, we have made little progress in chronic leukemia. Recently we have attempted some new treatments for chronic phase of CML, and confirmed those effectiveness. But for blastic crisis, we still grope in the dark. In this paper, we review the chemotherapy of CML and CLL including new treatments except bone marrow transplantation. PMID:2658837

  3. Childhood leukemia near nuclear plants in the United Kingdom: The evolution of a systematic approach to studying rare disease in small geographic areas

    SciTech Connect

    Beral, V. (I.C.R.F. Cancer Epidemiology Unit, Radcliffe Infirmary, Oxford (England))

    1990-07-01

    A cluster of childhood leukemia in a village near a nuclear plant in northern England prompted further studies of cancer in the vicinity of other nuclear plants in the United Kingdom. These studies demonstrated that the risk of childhood leukemia was increased near certain other nuclear plants. Although the reasons for the increase are still unclear, the scientific debate stimulated by these findings has clarified some of the special methodological problems encountered when studying rare diseases in small areas. Firstly, unless a specific hypothesis is defined in advance, the relevance of a single geographic cluster of disease can rarely be interpreted. Even when a prior hypothesis exists, the small number of cases which generally occur in a small area make the findings highly sensitive to reporting, diagnostic, or classification errors. The statistical power of such investigations is also usually low and only marked increases in risk can be detected. Furthermore, conventional statistical tests may be inappropriate if the underlying spatial distribution of the disease is not random; and little is known about the background distribution of disease in small areas. Investigations of specific hypotheses about defined sources of environmental contamination, especially if they can be replicated, are more likely to result in conclusive findings that are in-depth studies of individual clusters.

  4. Relativistic effects in the atomic and nuclear few-body problems

    SciTech Connect

    Friar, J.L.

    1980-01-01

    Relativistic effects in the atomic and nuclear few-body systems are classified and discussed with the emphasis on electromagnetic transitions. The size of relativistic corrections, calculational techniques and ambiguities, and comparison of theory and experiment are considered. 8 figures.

  5. HPV-16 E7 reveals a link between DNA replication stress, fanconi anemia D2 protein, and alternative lengthening of telomere-associated promyelocytic leukemia bodies.

    PubMed

    Spardy, Nicole; Duensing, Anette; Hoskins, Elizabeth E; Wells, Susanne I; Duensing, Stefan

    2008-12-01

    Expression of the high-risk human papillomavirus (HPV-16) E7 oncoprotein extends the life span of primary human keratinocytes and partially restores telomere length in the absence of telomerase. The molecular basis of this activity is incompletely understood. Here, we show that HPV-16 E7 induces an increased formation of alternative lengthening of telomeres (ALT)-associated promyelocytic leukemia bodies (APBs) in early passage primary human keratinocytes as well as HPV-negative tumor cells. This activity was found to require sequences of HPV-16 E7 involved in degradation of the retinoblastoma tumor suppressor protein as well as regions in the COOH terminus. HPV-16 E7-induced APBs contained ssDNA and several proteins that are involved in the response to DNA replication stress, most notably the Fanconi anemia D2 protein (FANCD2) as well as BRCA2 and MUS81. In line with these results, we found that FANCD2-containing APBs form in an ATR-dependent manner in HPV-16 E7-expressing cells. To directly show a role of FANCD2 in ALT, we provide evidence that knockdown of FANCD2 rapidly causes telomere dysfunction in cells that rely on ALT to maintain telomeres. Taken together, our results suggest a novel link between replication stress and recombination-based telomere maintenance that may play a role in HPV-16 E7-mediated extension of host cell life span and immortalization. PMID:19047177

  6. Self-association of Coilin Reveals a Common Theme in Nuclear Body Localization

    Microsoft Academic Search

    Michael D. Hebert; A. Gregory Matera

    We have found that coilin, the marker protein for Cajal bodies (coiled bodies, CBs), is a self- interacting protein, and we have mapped the domain responsible for this activity to the amino- terminus. Together with a nuclear localization signal, the self-interaction domain is necessary and sufficient for localization to CBs. Overexpression of various wild-type and mutant coilin con- structs in

  7. Nuclear-based techniques for the in vivo study of human body composition

    Microsoft Academic Search

    S H Cohn; R M Parr

    1985-01-01

    A variety of nuclear-based techniques for the in vivo study of human body decomposition is now available for clinical diagnosis and research, and the number of centres where such work is performed is likely to grow substantially in the next few years. Their most important applications at present are in the measurement of bone mineral mass (calcium), body protein (nitrogen)

  8. Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia.

    PubMed

    Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida R; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard T; Sandmaier, Brenda M; Estey, Elihu H; Appelbaum, Frederick R; Storer, Barry E; Deeg, Hans Joachim

    2014-04-01

    Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n = 36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n = 60: 35 first complete remission [CR], 18 second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14 g/m(2)/day treosulfan i.v. on days -6 to -4, 30 mg/m(2)/day fludarabine i.v. on days -6 to -2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n = 27) or unrelated (n = 69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n = 10) at the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS (41% versus 79%) at 2 years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse. PMID:24440648

  9. What Is Childhood Leukemia?

    MedlinePLUS

    ... key statistics for childhood leukemia? What is childhood leukemia? Cancer starts when cells start to grow out ... start making antibodies to fight them. Types of leukemia in children Leukemia is often described as being ...

  10. Drugs Approved for Leukemia

    MedlinePLUS

    ... Questions to Ask Your Doctor about Treatment Research Drugs Approved for Leukemia This page lists cancer drugs ... Hairy Cell Leukemia Drugs Approved for Meningeal Leukemia Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) ...

  11. Acute Lymphoblastic Leukemia

    MedlinePLUS

    ... Cancer Institute), www.leukemia-lymphoma.org (Leukemia and Lymphoma Society) or www.mayoclinic.com (Mayo Clinic). Type the keywords acute lymphoblastic leukemia or leukemia into the search box. Healing ...

  12. Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice?

    PubMed Central

    Uckun, Fatih M.; Myers, Dorothea E.; Ma, Hong; Rose, Rebecca; Qazi, Sanjive

    2015-01-01

    In high-risk remission B-precursor acute lymphoblastic leukemia (BPL) patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT) even after the use of very intensive total body irradiation (TBI)-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD) burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL”) fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI) combined with CD19L–sTRAIL was highly effective against (1) xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS) mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2) radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22?E12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT. PMID:26097891

  13. Multimer Formation Is Not Essential for Nuclear Export of Human T-Cell Leukemia Virus Type 1 Rex trans-Activator Protein

    PubMed Central

    Heger, Peter; Rosorius, Olaf; Koch, Claudia; Casari, Georg; Grassmann, Ralph; Hauber, Joachim

    1998-01-01

    The Rex trans-regulatory protein of human T-cell leukemia virus type 1 (HTLV-1) is required for the nuclear export of incompletely spliced and unspliced viral mRNAs and is therefore essential for virus replication. Rex is a nuclear phosphoprotein that directly binds to its cis-acting Rex response element RNA target sequence and constantly shuttles between the nucleus and cytoplasm. Moreover, Rex induces nuclear accumulation of unspliced viral RNA. Three protein domains which mediate nuclear import-RNA binding, nuclear export, and Rex oligomerization have been mapped within the 189-amino-acid Rex polypeptide. Here we identified a different region in the carboxy-terminal half of Rex which is also required for biological activity. In inactive mutants with mutations that map within this region, as well as in mutants that are deficient in Rex-specific multimerization, Rex trans activation could be reconstituted by fusion to a heterologous leucine zipper dimerization interface. The intracellular trafficking capabilities of wild-type and mutant Rex proteins reveal that biologically inactive and multimerization-deficient Rex mutants are still efficiently translocated from the nucleus to the cytoplasm. This observation indicates that multimerization is essential for Rex function but is not required for nuclear export. Finally, we are able to provide an improved model of the HTLV-1 Rex domain structure. PMID:9765406

  14. The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

    SciTech Connect

    Salsman, Jayme; Pinder, Jordan; Tse, Brenda [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Corkery, Dale [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada); Dellaire, Graham, E-mail: dellaire@dal.ca [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada)

    2013-10-15

    The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

  15. Dynamic Regulation of ARGONAUTE4 within Multiple Nuclear Bodies

    E-print Network

    Jacobsen, Steve

    ribosomal DNA (rDNA) sequences. AB-bodies also contain other proteins involved in RNA-directed DNA and transcriptional gene silencing at comple- mentary sequences in the genome [1­3]. Frequent targets of RdDM include transcriptional or post-transcriptional mechanisms [7,8]. In Arabidopsis, genes involved in the production of si

  16. A one-body transport model of fluctuation processes in nuclear collisions

    SciTech Connect

    Ayik, S. (Tennessee Technological Univ., Cookeville, TN (USA)); Gregoire, C.; Suraud, E.; Stryjewski, J.; Belkacem, M. (Grand Accelerateur National d'Ions Lourds (GANIL), 14 - Caen (France))

    1990-01-01

    Many aspects of a many-body system can be described in terms of one- body transport models in which the system at any time is characterized by its single-particle density rather than by the full many-body information. In these one-body models evaluation of the single-particle density is determined by a transport equation which contains the self-consistent mean-field potential and a collision term due to binary two-body collisions. Recently, this approach in a semi-classical limit with a Boltzmann-Uehling-Uhlenbeck (BUU) form of a collision term has been applied to nuclear collisions at intermediate energies. Common to all one-body models, only the average effects of two-body collisions are retained in the equation of motion and higher order correlations are entirely neglected. This approximation corresponds to an ensemble averaging which is evident, for example, from the molecular chaos assumption'' introduced in derivation of Boltzmann equation. As a result, these one-body models determine the ensemble averaged single-particle density and cannot provide a description for the fluctuation processes in nuclear collisions. On the other hand, at low and intermediate energies dynamical fluctuations are substantial due to large available phase space for decay into many final states. Therefore, it is of great interest to improve one-body transport models by incorporating dynamical fluctuations due to high order correlations into the equation of motion. 5 refs., 3 figs.

  17. Uncovering many-body correlations in nanoscale nuclear spin baths by central spin decoherence

    NASA Astrophysics Data System (ADS)

    Ma, Wen-Long; Wolfowicz, Gary; Zhao, Nan; Li, Shu-Shen; Morton, John J. L.; Liu, Ren-Bao

    2014-09-01

    Central spin decoherence caused by nuclear spin baths is often a critical issue in various quantum computing schemes, and it has also been used for sensing single-nuclear spins. Recent theoretical studies suggest that central spin decoherence can act as a probe of many-body physics in spin baths; however, identification and detection of many-body correlations of nuclear spins in nanoscale systems are highly challenging. Here, taking a phosphorus donor electron spin in a 29Si nuclear spin bath as our model system, we discover both theoretically and experimentally that many-body correlations in nanoscale nuclear spin baths produce identifiable signatures in decoherence of the central spin under multiple-pulse dynamical decoupling control. We demonstrate that under control by an odd or even number of pulses, the central spin decoherence is principally caused by second- or fourth-order nuclear spin correlations, respectively. This study marks an important step toward studying many-body physics using spin qubits.

  18. Uncovering many-body correlations in nanoscale nuclear spin baths by central spin decoherence

    PubMed Central

    Ma, Wen-Long; Wolfowicz, Gary; Zhao, Nan; Li, Shu-Shen; Morton, John J.L.; Liu, Ren-Bao

    2014-01-01

    Central spin decoherence caused by nuclear spin baths is often a critical issue in various quantum computing schemes, and it has also been used for sensing single-nuclear spins. Recent theoretical studies suggest that central spin decoherence can act as a probe of many-body physics in spin baths; however, identification and detection of many-body correlations of nuclear spins in nanoscale systems are highly challenging. Here, taking a phosphorus donor electron spin in a 29Si nuclear spin bath as our model system, we discover both theoretically and experimentally that many-body correlations in nanoscale nuclear spin baths produce identifiable signatures in decoherence of the central spin under multiple-pulse dynamical decoupling control. We demonstrate that under control by an odd or even number of pulses, the central spin decoherence is principally caused by second- or fourth-order nuclear spin correlations, respectively. This study marks an important step toward studying many-body physics using spin qubits. PMID:25205440

  19. The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis

    PubMed Central

    Smoyer, Christine J.; McCroskey, Scott; Miller, Brandon D.; Weaver, Kyle J.; Delventhal, Kym M.; Unruh, Jay; Slaughter, Brian D.; Jaspersen, Sue L.

    2011-01-01

    The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition. PMID:22125491

  20. PML Nuclear Bodies and SATB1 Are Associated with HLA Class I Expression in EBV+ Hodgkin Lymphoma

    PubMed Central

    Liu, Yuxuan; van den Berg, Anke; Veenstra, Rianne; Rutgers, Bea; Nolte, Ilja; van Imhoff, Gustaaf; Visser, Lydia; Diepstra, Arjan

    2013-01-01

    Tumor cells of classical Hodgkin lymphoma (cHL) are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML) and special AT-rich region binding protein 1 (SATB1) are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs) and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV? cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV? cases (p<0.0001). We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV? cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV? cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01). The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05). Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL. PMID:24009715

  1. The human T-cell leukemia virus type 1 transactivator protein Tax colocalizes in unique nuclear structures with NF-kappaB proteins.

    PubMed Central

    Bex, F; McDowall, A; Burny, A; Gaynor, R

    1997-01-01

    The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a potent activator of viral transcription. Tax also activates the expression of specific cellular genes involved in the control of T-lymphocyte growth via effects on cellular transcription factors, including members of the NF-kappaB/cRel family. Immunocytochemistry and electron microscopy were used to characterize the intracellular localization of Tax and identify cellular factors which are the potential targets for its transcriptional activity. These studies indicated that Tax localizes in discrete nuclear foci in T lymphocytes transformed by HTLV-1 and in cells transduced with Tax expression vectors. The Tax-containing foci are complex nuclear structures comprising a central core in which Tax colocalizes with splicing factor Sm. In addition to splicing factors Sm and SC-35, the Tax-containing nuclear structures also contain transcriptional components, including the largest subunit of RNA polymerase II and cyclin-dependent kinase CDK8. The inclusion of the two subunits of NF-kappaB, p50 and RelA, and the presence of the mRNA from a gene specifically activated by Tax through NF-kappaB binding sites suggest that these unique nuclear structures participate in Tax-mediated activation of gene expression via the NF-kappaB pathway. PMID:9094620

  2. Understanding Leukemia

    MedlinePLUS

    ... I 800.955.4572 I www.LLS.org Tracking Your Leukemia Tests These tips may help you ... Tyrosine kinase inhibitor (TKI). A drug that blocks cell growth. Gleevec®, Sprycel® and Tasigna® are TKIs that ... team consists of master’s level oncology professionals who are available by phone Monday through Friday, 9 am to 6 pm ( ...

  3. What Is Acute Myeloid Leukemia?

    MedlinePLUS

    ... get acute myeloid leukemia? What is acute myeloid leukemia? Leukemia is a type of cancer that starts ... person to bleed or bruise easily. Acute myeloid leukemia Acute myeloid leukemia (AML) goes by many names, ...

  4. What Is Chronic Myeloid Leukemia?

    MedlinePLUS

    ... about chronic myeloid leukemia? What is chronic myeloid leukemia? Chronic myeloid leukemia (CML), also known as chronic ... is the same as for adults. What is leukemia? Leukemia is a cancer that starts in the ...

  5. Modifications of single-particle properties in nuclear matter induced by three-body forces

    E-print Network

    V. Soma; P. Bozek

    2008-11-25

    Within the self-consistent Green's functions formalism, we study the effects of three-body forces on the in-medium spectral function, self-energy and effective mass of the nuclear matter constituents, analyzing the density and momentum dependence.

  6. Positronium formation as a three-body reaction. II. The second-order nuclear amplitudes

    SciTech Connect

    Shojaei, F.; Bolorizadeh, M. A. [Physics Department, Shahid Bahonar University of Kerman, Kerman, 76169, Iran and ICST, Mahan, 76315 (Iran, Islamic Republic of); Ghanbari-Adivi, E. [Physics Department and Isfahan Quantum Optics Group, University of Isfahan, Isfahan, 81746 (Iran, Islamic Republic of); Brunger, M. J. [Centre for Antimatter-Matter Studies, School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide South Australia, 5042 (Australia)

    2009-01-15

    We derive an exact analytic form for the second-order nuclear amplitudes, under the Faddeev three-body approach, which is applicable to the nonrelativistic high energy impact interaction where positronium is formed in the collision of a positron with an atom.

  7. Leaf phenolic inhibition of gypsy moth nuclear polyhedrosis virus Role of polyhedral inclusion body aggregation

    Microsoft Academic Search

    Steven T. Keating; Mark D. Hunter; Jack C. Schultz

    1990-01-01

    Bioassays with nuclear polyhedrosis virus (NPV) administered to gypsy moth larvae on leaf disks from various tree species reveal strong viral inhibition by some tree species. Phenolic extracts from inhibitory tree leaves cause virus polyhedral inclusion bodies (PIBs) to form large aggregations. However, aggregated PIBs treated with leaf extracts and administered to larvae on laboratory diet (without phenolics) retain virulence.

  8. An Effective Theory for Nuclear Matter with Genuine Many-Body Forces

    NASA Astrophysics Data System (ADS)

    Vasconcellos, César A. Z.; Horvath, Jorge; Hadjimichef, Dimiter; Gomes, Rosana O.

    Nuclear science has developed many excellent descriptions that embody various properties of the nucleus, and nuclear matter at low, medium and high densities. However, a full microscopic understanding of nuclear systems is still lacking. The aim of our theoretical research group is to shed some light on such challenges and particularly on open questions facing the high density nuclear many-body problem. Here we focus our attention on the conceptual issue of naturalness and its role in shaping the baryon-meson phase space dynamics in the description of the equation of state (EoS) of nuclear matter. In particular, in order to stimulate possible new directions of research, we discuss relevant aspects of a recently developed relativistic effective theory for nuclear matter with natural parametric couplings and genuine many-body forces. Among other topics we discuss in this work the connection of this theory with other known effective QHD models of the literature and its potentiality in describing a new physics for dense matter.

  9. Understanding Leukemias

    NSDL National Science Digital Library

    Braun, Mark

    This tutorial is designed to aid medical students at all levels understand the laboratory diagnosis of leukemias. It includes introductory material on the basic laboratory tests specific to diagnoses, their general application and pitfalls in interpretation. The introductory material is followed by a series of short clinical vignettes illustrating the major categories of leukemia. This tutorial focuses on diagnosis and relative little on treatment is included. QuickTime movie player, Flash player and Java script runtime plug-in scripts are required for some pages. The tutorial concludes with a short self-help quiz covering the major points developed. The plug-ins noted above are available free at the following sites: http://www.apple.com/quicktime/download/win.html and http://www.sun.com/ . Questions should be directed to Dr. Mark Braun; braunm@indiana.edu.Annotated: falseDisease diagnosis: neoplastic

  10. Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells

    PubMed Central

    Poh, Yeh-Chuin; Shevtsov, Sergey P.; Chowdhury, Farhan; Wu, Douglas C.; Na, Sungsoo; Dundr, Miroslav; Wang, Ning

    2012-01-01

    Despite past progress in understanding mechanisms of cellular mechanotransduction, it is unclear whether a local surface force can directly alter nuclear functions without intermediate biochemical cascades. Here we show that a local dynamic force via integrins resulted in direct displacements of coilin and SMN proteins in Cajal bodies (CBs) and direct dissociation of coilin-SMN complexes. Spontaneous movements of coilin increased more than those of SMN in the same CB after dynamic force application. FRET changes of coilin-SMN depended on force magnitude, an intact F-actin, cytoskeletal tension, Lamin A/C, or substrate rigidity. Other protein pairs in CBs exhibited different magnitudes of FRET. Dynamic cyclic force induced tiny phase lags between various protein pairs in CBs, suggesting viscoelastic interactions between them. These findings demonstrate that dynamic force-induced direct structural changes of protein complexes in Cajal bodies may represent a unique mechanism of mechanotransduction that impacts on nuclear functions involved in gene expression. PMID:22643893

  11. Stages of Chronic Lymphocytic Leukemia

    MedlinePLUS

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®) General Information About Chronic Lymphocytic Leukemia Key Points Chronic lymphocytic leukemia is a type ...

  12. RNA recognition motif 2 directs the recruitment of SF2\\/ASF to nuclear stress bodies

    Microsoft Academic Search

    Ilaria Chiodi; Margherita Corioni; Manuela Giordano; Rut Valgardsdottir; Claudia Ghigna; Fabio Cobianchi; Rui-Ming Xu; Silvano Riva; Giuseppe Biamonti

    2004-01-01

    Heat shock induces the transcriptional activation of large heterochromatic regions of the human genome composed of arrays of satellite III DNA repeats. A num- ber of RNA-processing factors, among them splicing factor SF2\\/ASF, associate with these transcription factors giving rise to nuclear stress bodies (nSBs). Here, we show that the recruitment of SF2\\/ASF to these structures is mediated by its

  13. One-body Properties of Nuclear Matter with Off-shell Propagation

    E-print Network

    P. Bozek

    2002-01-31

    Symmetric nuclear matter is studied in the self-consistent, in-medium $T$-matrix approach. One-body spectral function, optical potential, and scattering width are calculated. Properties of quasi-particle excitations at the Fermi surface are discussed. Dispersive self-energies are dominated by contributions from the $^1S_0$, $3S_1-^3D_1$, and $^3P_1$ partial waves.

  14. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha

    Microsoft Academic Search

    Jin Fu; Silvana Gaetani; Fariba Oveisi; Jesse Lo Verme; Antonia Serrano; Fernando Rodríguez de Fonseca; Anja Rosengarth; Hartmut Luecke; Barbara Di Giacomo; Giorgio Tarzia; Daniele Piomelli

    2003-01-01

    Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor that regulates several aspects of lipid metabolism.

  15. Disruption of PML-associated nuclear bodies during human cytomegalovirus infection.

    PubMed

    Kelly, C; Van Driel, R; Wilkinson, G W

    1995-11-01

    PML is a protein associated with discrete spherical structures within the nucleus of normal cells. A defect in PML expression is observed in acute promyelocytic leukaemia as a consequence of a chromosomal translocation involving the genes encoding PML and the alpha retinoic acid receptor (RAR alpha). Disruption of PML bodies also occurs during herpes simplex virus infection after the immediate early protein Vmw110 has become associated with PML bodies. In this study, we followed the fate of PML bodies in human fibroblasts during the course of a human cytomegalovirus (CMV) infection. Disruption of PML bodies was observed to be dependent on de novo CMV gene expression and to occur within 4 h post-infection, concomitant with the onset of CMV IE gene expression. Although a transient increase in the number of PML bodies could be observed in some cells, PML exists predominantly as a diffuse nuclear protein during both the early and late stages of CMV infection. Although the function of PML bodies is still uncertain, their disruption may be important for efficient herpes virus replication. PMID:7595400

  16. Nuclear-matter equation of state with consistent two- and three-body perturbative chiral interactions

    NASA Astrophysics Data System (ADS)

    Coraggio, L.; Holt, J. W.; Itaco, N.; Machleidt, R.; Marcucci, L. E.; Sammarruca, F.

    2014-04-01

    We compute the energy per particle of infinite symmetric nuclear matter from chiral NLO3 (next-to-next-to-next-to-leading order) two-body potentials plus NLO2 three-body forces. The low-energy constants of the chiral three-nucleon force that cannot be constrained by two-body observables are fitted to reproduce the triton binding energy and the H3-He3 Gamow-Teller transition matrix element. In this way, the saturation properties of nuclear matter are reproduced in a parameter-free approach. The equation of state is computed up to third order in many-body perturbation theory, with special emphasis on the role of the third-order particle-hole diagram. The dependence of these results on the cutoff scale and regulator function is studied. We find that the inclusion of three-nucleon forces consistent with the applied two-nucleon interaction leads to a reduced dependence on the choice of the regulator only for lower values of the cutoff.

  17. Tax protein of human T-cell leukemia virus type I binds to the ankyrin motifs of inhibitory factor kappa B and induces nuclear translocation of transcription factor NF-kappa B proteins for transcriptional activation.

    PubMed Central

    Hirai, H; Suzuki, T; Fujisawa, J; Inoue, J; Yoshida, M

    1994-01-01

    Human T-cell leukemia virus type I causes adult T-cell leukemia and tropical spastic paraparesis, and its regulator protein Tax has been implicated in the pathogenic activity of human T-cell leukemia virus type I. Tax activates transcription of viral and cellular genes through specific enhancers: the 21-bp enhancer of human T-cell leukemia virus type I, the nuclear factor kappa B (NF-kappa B)-binding site of the interleukin 2 receptor alpha gene, and the serum-responsive element of c-fos. Tax binds to enhancer-binding proteins including cAMP-responsive element-binding protein, cAMP-responsive element modulator, transcription factor NF-kappa B p50 and p67SRF, and associates with each enhancer DNA indirectly. In addition to this mechanism, we report here that Tax binds to inhibitory factor kappa B gamma (I-kappa B) gamma, which forms a complex with NF-kappa B protein heterodimer p50-p65 or homodimer p50-p50 and retains them in the cytoplasm. Tax binding to I-kappa B gamma induces nuclear translocation of NF-kappa B p65. In association with this nuclear translocation of p65, transcription directed by the kappa B enhancer is strongly activated. Tax binds to the ankyrin motifs of I-kappa B gamma, suggesting its possible interaction with many other proteins carrying ankyrin motifs contributing to various regulatory processes. This is a different mechanism of transcriptional activation by the oncoprotein Tax and seems to be independent from the trans-activation through indirect binding to enhancer DNAs. Images PMID:8170951

  18. PODs in the Nuclear Spot: Enigmas in the Magician's Pot

    NSDL National Science Digital Library

    Mitsutoki Hatta (University of Tsukuba; Center for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry REV)

    2001-08-21

    The promyelocytic leukemia (PML) nuclear body, also known as the PML oncogenic domain (POD), is implicated in the pathophysiology of PML. These nuclear subcompartments are dynamic structures. The PML protein, which undergoes a fusion event in patients with promyelocytic leukemia, is normally found in PODs. The PML protein may be a major regulator of the constituents of PODs, controlling POD organization and function. Hatta and Fukamizu describe the functions of PML and discuss how the POD structure and organization may be regulated and affect apoptosis, gene expression, and cellular transformation.

  19. Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus

    SciTech Connect

    Sorensen, Karina Dalsgaard [Department of Molecular Biology, University of Aarhus, C.F. Mollers Alle, Building 130, DK-8000 Aarhus C (Denmark); Sorensen, Annette Balle [Department of Molecular Biology, University of Aarhus, C.F. Mollers Alle, Building 130, DK-8000 Aarhus C (Denmark); Quintanilla-Martinez, Leticia [Institute of Pathology, GSF-National Research Center for Environment and Health, Neuherberg (Germany); Kunder, Sandra [Institute of Pathology, GSF-National Research Center for Environment and Health, Neuherberg (Germany); Schmidt, Joerg [Department of Comparative Medicine, GSF-National Research Center for Environment and Health, Neuherberg (Germany); Pedersen, Finn Skou [Department of Molecular Biology, University of Aarhus, C.F. Mollers Alle, Building 130, DK-8000 Aarhus C (Denmark) and Department of Medical Microbiology and Immunology, University of Aarhus (Denmark)]. E-mail: fsp@mb.au.dk

    2005-04-10

    Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity.

  20. Childhood Cancer: Leukemia (For Parents)

    MedlinePLUS

    About Leukemia The term leukemia refers to cancers of the white blood cells (also called leukocytes or WBCs). When ... the disease without it coming back. Types of Leukemia In general, leukemias are classified into acute (rapidly ...

  1. The Relationship between SMN, the Spinal Muscular Atrophy Protein, and Nuclear Coiled Bodies in Differentiated Tissues and Cultured Cells

    Microsoft Academic Search

    Philip J. Young; Thanh T. Le; Nguyen thi Man; Arthur H. M. Burghes; Glenn E. Morris

    2000-01-01

    The spinal muscular atrophy protein, SMN, is a cytoplasmic protein that is also found in distinct nuclear structures called “gems.” Gems are closely associated with nuclear coiled bodies and both may have a direct role in snRNP maturation and pre-RNA splicing. There has been some controversy over whether gems and coiled bodies colocalize or form adjacent\\/independent structures in HeLa and

  2. Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication

    PubMed Central

    Kupke, Thomas; Di Cecco, Leontina; Müller, Hans-Michael; Neuner, Annett; Adolf, Frank; Wieland, Felix; Nickel, Walter; Schiebel, Elmar

    2011-01-01

    Spindle pole bodies (SPBs), like nuclear pore complexes, are embedded in the nuclear envelope (NE) at sites of fusion of the inner and outer nuclear membranes. A network of interacting proteins is required to insert a cytoplasmic SPB precursor into the NE. A central player of this network is Nbp1 that interacts with the conserved integral membrane protein Ndc1. Here, we establish that Nbp1 is a monotopic membrane protein that is essential for SPB insertion at the inner face of the NE. In vitro and in vivo studies identified an N-terminal amphipathic ?-helix of Nbp1 as a membrane-binding element, with crucial functions in SPB duplication. The karyopherin Kap123 binds to a nuclear localization sequence next to this amphipathic ?-helix and prevents unspecific tethering of Nbp1 to membranes. After transport into the nucleus, Nbp1 binds to the inner nuclear membrane. These data define the targeting pathway of a SPB component and suggest that the amphipathic ?-helix of Nbp1 is important for SPB insertion into the NE from within the nucleus. PMID:21785410

  3. Yields of Soviet underground nuclear explosions at Novaya Zemlya, 1964-1976, from seismic body and surface waves

    Microsoft Academic Search

    L. R. Sykes; G. C. Wiggins

    1986-01-01

    Surface and body wave magnitudes are determined for 15 USSR underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (m\\/sub b\\/) values indicates a clustering of explosions at a few specific yields. The

  4. Yields of Soviet Underground Nuclear Explosions at Novaya Zemlya, 1964-1976, from Seismic Body and Surface Waves

    Microsoft Academic Search

    Lynn R. Sykes; Graham C. Wiggins

    1986-01-01

    Surface and body wave magnitudes are determined for 15 U.S.S.R. underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (mb) values indicates a clustering of explosions at a few specific yields. The most

  5. A nuclear many-body theory at finite temperature applied to protoneutron star

    E-print Network

    Guilherme F. Marranghello; Cesar A. Z. Vasconcellos; Manfred Dillig

    2002-05-13

    Thermodynamical properties of nuclear matter are studied in the framework of an effective many-body field theory at finite temperature, considering the Sommerfeld approximation. We perform the calculations by using the nonlinear Boguta and Bodmer model, extended by the inclusion of the fundamental baryon octet and leptonic degrees of freedom. Trapped neutrinos are included in order to describe protoneutron star properties through the integration of the Tolman-Oppenheimer-Volkoff equations, from which we obtain, beyond the standard plots for the mass and radius of the protoneutron stars as functions of central density, new plots of these quantities as functions of temperature. Our predictions include the determination of an absolute value for the limiting protoneutron star mass; new aspects on nuclear matter phase transition via the behaviour of the specific heat and, through the inclusion of quark degrees of freedom, the properties of a hadron-quark phase transition and of the hybrid protoneutron stars.

  6. Nuclear three-body problem in the complex energy plane: Complex-Scaling-Slater method

    E-print Network

    A. T. Kruppa; G. Papadimitriou; W. Nazarewicz; N. Michel

    2013-10-29

    The physics of open quantum systems is an interdisciplinary area of research. The nuclear "openness" manifests itself through the presence of the many-body continuum representing various decay, scattering, and reaction channels. As the radioactive nuclear beam experimentation extends the known nuclear landscape towards the particle drip lines, the coupling to the continuum space becomes exceedingly more important. Of particular interest are weakly bound and unbound nuclear states appearing around particle thresholds. Theories of such nuclei must take into account their open quantum nature. To describe open quantum systems, we introduce a Complex Scaling (CS) approach in the Slater basis. We benchmark it with the complex-energy Gamow Shell Model (GSM) by studying energies and wave functions of the bound and unbound states of the two-neutron halo nucleus 6He viewed as an $\\alpha$+ n + n cluster system. In the CS approach, we use the Slater basis, which exhibits the correct asymptotic behavior at large distances. To extract particle densities from the back-rotated CS solutions, we apply the Tikhonov regularization procedure, which minimizes the ultraviolet numerical noise. While standard applications of the inverse complex transformation to the complex-rotated solution provide unstable results, the stabilization method fully reproduces the GSM benchmark. We also propose a method to determine the smoothing parameter of the Tikhonov regularization. The combined suite of CS-Slater and GSM techniques has many attractive features when applied to nuclear problems involving weakly-bound and unbound states. While both methods can describe energies, total widths, and wave functions of nuclear states, the CS-Slater method, if it can be applied, can provide an additional information about partial energy widths associated with individual thresholds.

  7. Acute Myeloid Leukemia

    MedlinePLUS

    ... myeloblasts or myeloid blasts. These cells do not mature into healthy blood cells. Instead, they develop into ... types of leukemia cells or help leukemia cells mature into white blood cells. These drugs are used ...

  8. Acute Lymphocytic Leukemia

    MedlinePLUS

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  9. A Snapshot of Leukemia

    MedlinePLUS

    ... CML ). Although leukemia occurs most often in older adults, it is among the most common childhood cancers. ... contrast, the most common types of leukemia in adults are AML and CLL, followed by ALL and ...

  10. The relationship between SMN, the spinal muscular atrophy protein, and nuclear coiled bodies in differentiated tissues and cultured cells.

    PubMed

    Young, P J; Le, T T; thi Man, N; Burghes, A H; Morris, G E

    2000-05-01

    The spinal muscular atrophy protein, SMN, is a cytoplasmic protein that is also found in distinct nuclear structures called "gems." Gems are closely associated with nuclear coiled bodies and both may have a direct role in snRNP maturation and pre-RNA splicing. There has been some controversy over whether gems and coiled bodies colocalize or form adjacent/independent structures in HeLa and other cultured cells. Using a new panel of antibodies against SMN and antibodies against coilin-p80, a systematic and quantitative study of adult differentiated tissues has shown that gems always colocalize with coiled bodies. In some tissues, a small proportion of coiled bodies (<10%) had no SMN, but independent or adjacent gems were not found. The most striking observation, however, was that many cell types appear to have neither gems nor coiled bodies (e.g., cardiac and smooth muscle, blood vessels, stomach, and spleen) and this expression pattern is conserved across human, rabbit, and pig species. This shows that assembly of distinct nuclear bodies is not essential for RNA splicing and supports the view that they may be storage sites for reserves of essential proteins and snRNPs. Overexpression of SMN in COS-7 cells produced supernumerary nuclear bodies, most of which also contained coilin-p80, confirming the close relationship between gems and coiled bodies. However, when SMN is reduced to very low levels in type I SMA fibroblasts, coiled bodies are still formed. Overall, the data suggest that gem/coiled body formation is not determined by high cytoplasmic SMN concentrations or high metabolic activity alone and that a differentiation-specific factor may control their formation. PMID:10772809

  11. Human T-cell leukemia virus type I p30 nuclear/nucleolar retention is mediated through interactions with RNA and a constituent of the 60 S ribosomal subunit.

    PubMed

    Ghorbel, Sofiane; Sinha-Datta, Uma; Dundr, Miroslav; Brown, Megan; Franchini, Genoveffa; Nicot, Christophe

    2006-12-01

    Human T-cell leukemia virus type I is the etiological agent of adult T-cell leukemia/lymphoma, an aggressive and fatal lymphoproliferative malignancy. The virus has evolved strategies to escape immune clearance by remaining latent in most infected cells in vivo. We demonstrated previously that virally encoded p30 protein is a potent post-transcriptional inhibitor of virus replication (Nicot, C., Dundr, M., Johnson, J. M., Fullen, J. R., Alonzo, N., Fukumoto, R., Princler, G. L., Derse, D., Misteli, T., and Franchini, G. (2004) Nat. Med. 10, 197-201). p30 is unable to shuttle out of the nucleus in heterokaryon assays, suggesting the existence of specific retention signals. Because suppression of virus replication relies on nuclear retention of the tax/rex mRNA by p30, determining the retention features of p30 will offer hints to break latency in infected cells and insights into new therapeutic approaches. In this study, we used live cell imaging technologies to study the kinetics of p30 and to delineate its retention signals and their function in virus replication. Notably, this is the first study to identify p30 nucleolar retention domains. Using mutants of p30 that localized in different cellular compartments, we show that post-transcriptional control of virus replication by p30 occurs in the nucleoplasm. We further demonstrate that p30 nuclear/nucleolar retention is dependent upon de novo RNA transcripts and interactions with components of the ribosomal machinery. PMID:17008317

  12. Low-temperature triple-alpha rate in a full three-body nuclear model.

    PubMed

    Nguyen, N B; Nunes, F M; Thompson, I J; Brown, E F

    2012-10-01

    A new three-body method is used to compute the rate of the triple-alpha capture reaction, which is the primary source of 12C in stars. In this Letter, we combine the Faddeev hyperspherical harmonics and the R-matrix method to obtain a full solution to the three-body ?+?+? continuum. Particular attention is paid to the long-range effects caused by the pairwise Coulomb interactions. The new rate agrees with the Nuclear Astrophysics Compilation of Reaction rates for temperatures greater than 0.07 GK, but a large enhancement at lower temperature is found (?10(12) at 0.02 GK). Our results are compared to previous calculations where additional approximations were made. We show that the new rate does not significantly change the evolution of stars around one solar mass. In particular, such stars still undergo a red-giant phase consistent with observations, and no significant differences are found in the final white dwarfs. PMID:23083232

  13. Nuf2, a spindle pole body-associated protein required for nuclear division in yeast

    PubMed Central

    1994-01-01

    The NUF2 gene of the yeast Saccharomyces cerevisiae encodes an essential 53-kd protein with a high content of potential coiled-coil structure similar to myosin. Nuf2 is associated with the spindle pole body (SPB) as determined by coimmunofluorescence with known SPB proteins. Nuf2 appears to be localized to the intranuclear region and is a candidate for a protein involved in SPB separation. The nuclear association of Nuf2 can be disrupted, in part, by 1 M salt but not by the detergent Triton X-100. All Nuf2 can be removed from nuclei by 8 M urea extraction. In this regard, Nuf2 is similar to other SPB- associated proteins including Nufl/SPC110, also a coiled-coil protein. Temperature-sensitive alleles of NUF2 were generated within the coiled- coil region of Nuf2 and such NUF2 mutant cells rapidly arrest after temperature shift with a single undivided or partially divided nucleus in the bud neck, a shortened mitotic spindle and their DNA fully replicated. In sum, Nuf2 is a protein associated with the SPB that is critical for nuclear division. Anti-Nuf2 antibodies also recognize a mammalian 73-kd protein and display centrosome staining of mammalian tissue culture cells suggesting the presence of a protein with similar function. PMID:8188751

  14. An Introductory Guide to GREEN’S Function Methods in Nuclear Many-Body Problems

    NASA Astrophysics Data System (ADS)

    Kuo, T. T. S.; Tzeng, Yiharn

    We present an elementary and fairly detailed review of several Green’s function methods for treating nuclear and other many-body systems. We first treat the single-particle Green’s function, by way of which some details concerning linked diagram expansion, rules for evaluating Green’s function diagrams and solution of the Dyson’s integral equation for Green’s function are exhibited. The particle-particle hole-hole (pphh) Green’s function is then considered, and a specific time-blocking technique is discussed. This technique enables us to have a one-frequency Dyson’s equation for the pphh and similarly for other Green’s functions, thus considerably facilitating their calculation. A third type of Green’s function considered is the particle-hole Green’s function. RPA and high order RPA are treated, along with examples for setting up particle-hole RPA equations. A general method for deriving a model-space Dyson’s equation for Green’s functions is discussed. We also discuss a method for determining the normalization of Green’s function transition amplitudes based on its vertex function. Some applications of Green’s function methods to nuclear structure and recent deep inelastic lepton-nucleus scattering are addressed.

  15. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    SciTech Connect

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  16. Formation of nuclear bodies by the lncRNA Gomafu-associating proteins Celf3 and SF1

    PubMed Central

    Ishizuka, Akira; Hasegawa, Yuko; Ishida, Kentaro; Yanaka, Kaori; Nakagawa, Shinichi

    2014-01-01

    Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes. However, how Gomafu controls these biological processes at the molecular level has remained largely unknown. In this study, we identified the RNA-binding protein Celf3 as a novel Gomafu-associating protein. Knockdown of Celf3 led to the down-regulation of Gomafu, and cross-link RNA precipitation analysis confirmed specific binding between Celf3 and Gomafu. In the neuroblastoma cell line Neuro2A, Celf3 formed novel nuclear bodies (named CS bodies) that colocalized with SF1, another Gomafu-binding protein. Gomafu, however, was not enriched in the CS bodies; instead, it formed distinct nuclear bodies in separate regions in the nucleus. These observations suggest that Gomafu indirectly modulates the function of the splicing factors SF1 and Celf3 by sequestering these proteins into separate nuclear bodies. PMID:25145264

  17. In medium T-matrix for nuclear matter with three-body forces - binding energy and single particle properties

    E-print Network

    V. Soma; P. Bozek

    2008-08-21

    We present spectral calculations of nuclear matter properties including three-body forces. Within the in-medium T-matrix approach, implemented with the CD-Bonn and Nijmegen potentials plus the three-nucleon Urbana interaction, we compute the energy per particle in symmetric and neutron matter. The three-body forces are included via an effective density dependent two-body force in the in-medium T-matrix equations. After fine tuning the parameters of the three-body force to reproduce the phenomenological saturation point in symmetric nuclear matter, we calculate the incompressibility and the energy per particle in neutron matter. We find a soft equation of state in symmetric nuclear matter but a relatively large value of the symmetry energy. We study the the influence of the three-body forces on the single-particle properties. For symmetric matter the spectral function is broadened at all momenta and all densities, while an opposite effect is found for the case of neutrons only. Noticeable modification of the spectral functions are realized only for densities above the saturation density. The modifications of the self-energy and the effective mass are not very large and appear to be strongly suppressed above the Fermi momentum.

  18. In-medium T matrix for nuclear matter with three-body forces: Binding energy and single-particle properties

    SciTech Connect

    Soma, V. [Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland); Bozek, P. [Institute of Physics, Rzeszow University, PL-35-959 Rzeszow (Poland); Institute of Nuclear Physics PAN, PL-31-342 Krakow (Poland)

    2008-11-15

    We present spectral calculations of nuclear matter properties including three-body forces. Within the in-medium T-matrix approach, implemented with the CD-Bonn and Nijmegen potentials plus the three-nucleon Urbana interaction, we compute the energy per particle in symmetric and neutron matter. The three-body forces are included via an effective density dependent two-body force in the in-medium T-matrix equations. After fine tuning the parameters of the three-body force to reproduce the phenomenological saturation point in symmetric nuclear matter, we calculate the incompressibility and the energy per particle in neutron matter. We find a soft equation of state in symmetric nuclear matter but a relatively large value of the symmetry energy. We study the the influence of the three-body forces on the single-particle properties. For symmetric matter the spectral function is broadened at all momenta and all densities, while an opposite effect is found for the case of neutrons only. Noticeable modification of the spectral functions are realized only for densities above the saturation density. The modifications of the self-energy and the effective mass are not very large and appear to be strongly suppressed above the Fermi momentum.

  19. RNA-related nuclear functions of human Pat1b, the P-body mRNA decay factor

    PubMed Central

    Marnef, Aline; Weil, Dominique; Standart, Nancy

    2012-01-01

    The evolutionarily conserved Pat1 proteins are P-body components recently shown to play important roles in cytoplasmic gene expression control. Using human cell lines, we demonstrate that human Pat1b is a shuttling protein whose nuclear export is mediated via a consensus NES sequence and Crm1, as evidenced by leptomycin B (LMB) treatment. However, not all P-body components are nucleocytoplasmic proteins; rck/p54, Dcp1a, Edc3, Ge-1, and Xrn1 are insensitive to LMB and remain cytoplasmic in its presence. Nuclear Pat1b localizes to PML–associated foci and SC35-containing splicing speckles in a transcription-dependent manner, whereas in the absence of RNA synthesis, Pat1b redistributes to crescent-shaped nucleolar caps. Furthermore, inhibition of splicing by spliceostatin A leads to the reorganization of SC35 speckles, which is closely mirrored by Pat1b, indicating that it may also be involved in splicing processes. Of interest, Pat1b retention in these three nuclear compartments is mediated via distinct regions of the protein. Examination of the nuclear distribution of 4E-T(ransporter), an additional P-body nucleocytoplasmic protein, revealed that 4E-T colocalizes with Pat1b in PML-associated foci but not in nucleolar caps. Taken together, our findings strongly suggest that Pat1b participates in several RNA-related nuclear processes in addition to its multiple regulatory roles in the cytoplasm. PMID:22090346

  20. PREFACE: Many-body correlations from dilute to dense nuclear systems

    NASA Astrophysics Data System (ADS)

    Otsuka, Takaharu; Urban, Michael; Yamada, Taiichi

    2011-09-01

    The International EFES-IN2P3 conference on "Many body correlations from dilute to dense nuclear systems" was held at the Institut Henri Poincaré (IHP), Paris, France, from 15-18 February 2011, on the occasion of the retirement of our colleague Peter Schuck. Correlations play a decisive role in various many-body systems such as nuclear systems, condensed matter and quantum gases. Important examples include: pairing correlations (Cooper pairs) which give rise to nuclear superfluidity (analogous to superconductivity in condensed matter); particle-hole (RPA) correlations in the description of the ground state beyond mean-field theory; clusters; and ?-particle correlations in certain nuclei. Also, the nucleons themselves can be viewed as clusters of three quarks. During the past few years, researchers have started to study how the character of these correlations changes with the variation of the density. For instance, the Cooper pairs in dense matter can transform into a Bose-Einstein condensate (BEC) of true bound states at low density (this is the BCS-BEC crossover studied in ultracold Fermi gases). Similar effects play a role in neutron matter at low density, e.g., in the "neutron skin" of exotic nuclei. The ?-cluster correlation becomes particularly important at lower density, such as in the excited states of some nuclei (e.g., the ?-condensate-like structure in the Hoyle state of 12C) or in the formation of compact stars. In addition to nuclear physics, topics from astrophysics (neutron stars), condensed matter, and quantum gases were discussed in 48 talks and 19 posters, allowing the almost 90 participants from different communities to exchange their ideas, experiences and methods. The conference dinner took place at the Musée d'Orsay, and all the participants enjoyed the very pleasant atmosphere. One session of the conference was dedicated to the celebration of Peter's retirement. We would like to take this opportunity to wish Peter all the best and we hope that he will continue his scientific work full of creative and original ideas. We would like to thank all those who helped to make the conference a success: Nguyen van Giai, S Fujii, J Margueron, K Hagino, and Y Kanada-En'yo for their help with the organization; the advisory committee for suggesting invited speakers; V Frois for her administrative help; L Petizon for the website; and the director of IPN Orsay, F Azaiez, for his support. We are indebted to IHP for providing the lecture hall free of charge, and we acknowledge the financial support from JSPS through its EFES core-to-core program, from CNRS (IN2P3 and INP), and from LIA France-Japon. Last but not least, we are grateful to all of the participants for making the conference exciting and successful. Takaharu Otsuka, Michael Urban, Taiichi YamadaEditors of the proceedings

  1. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  2. Exclusive Ubiquitination and Sumoylation on Overlapping Lysine Residues Mediate NF-?B Activation by the Human T-Cell Leukemia Virus Tax Oncoprotein†

    PubMed Central

    Lamsoul, Isabelle; Lodewick, Julie; Lebrun, Sylvie; Brasseur, Robert; Burny, Arsène; Gaynor, Richard B.; Bex, Françoise

    2005-01-01

    The transcription factor NF-?B is critical for the induction of cancer, including adult T-cell leukemia, which is linked to infection by human T-cell leukemia virus type 1 and the expression of its regulatory protein Tax. Although activation of the NF-?B pathway by Tax involves its interaction with the regulatory subunit of the I?B kinase (IKK) complex, NEMO/IKK?, the mechanism by which Tax activates specific cellular genes in the nucleus remains unknown. Here, we demonstrate that the attachment of SUMO-1 to Tax regulates its localization in nuclear bodies and the recruitment of both the RelA subunit of NF-?B and free IKK? in these nuclear structures. However, this sumoylation step is not sufficient for the activation of the NF-?B pathway by Tax. This activity requires the prior ubiquitination and colocalization of ubiquitinated Tax with IKK complexes in the cytoplasm and the subsequent migration of the RelA subunit of NF-?B to the nucleus. Thus, the ubiquitination and sumoylation of Tax function in concert to result in the migration of RelA to the nucleus and its accumulation with IKK? in nuclear bodies for activation of gene expression. These modifications may result in targets for the treatment of adult T-cell leukemia. PMID:16287853

  3. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  4. ACUTE LEUKEMIAS ACUTE MYELOGENOUS

    E-print Network

    Trisomy 8(+8), t(9;22), t(6;9) 90% myeloblasts AML-M2 Acute Myeloblastic Leukemia with Maturation Black B, & Choloacetate Esterase t(8;21) #12;9/16/2013 4 AML-M3 Acute Promyelocytic Leukemia between chromosomes 8 and 21 AML with a translocation or inversion in chromosome 16 AML with changes

  5. The Role of Three-Nucleon Forces and Many-Body Processes in Nuclear Pairing

    SciTech Connect

    Holt, Jason D. [Technische Univ. Darmstadt/GSI/UTK/ORNL; Menendez, J. [Technische Univ. Darmstadt/GSI Helmholtzzentrum fur Schweionenforschung, Germany; Schwenk, A. [Technische Univ. Darmstadt/GSI Helmholtzzentrum fur Schweionenforschung, Germany

    2013-01-01

    We present microscopic valence-shell calculations of pairing gaps in the calcium isotopes, focusing on the role of three-nucleon (3N) forces and manybody processes. In most cases, we find a reduction in pairing strength when the leading chiral 3N forces are included, compared to results with lowmomentum two-nucleon (NN) interactions only. This is in agreement with a recent energy density functional study. At the NN level, calculations that include particle particle and hole hole ladder contributions lead to smaller pairing gaps compared with experiment. When particle hole contributions as well as the normal-ordered one- and two-body parts of 3N forces are consistently included to third order, we find reasonable agreement with experimental three-point mass differences. This highlights the important role of 3N forces and manybody processes for pairing in nuclei. Finally, we relate pairing gaps to the evolution of nuclear structure in neutron-rich calcium isotopes and study the predictions for the 2+ excitation energies, in particular for 54Ca.

  6. Light clusters in nuclear matter: Excluded volume versus quantum many-body approaches

    E-print Network

    Matthias Hempel; Jürgen Schaffner-Bielich; Stefan Typel; Gerd Röpke

    2011-11-23

    The formation of clusters in nuclear matter is investigated, which occurs e.g. in low energy heavy ion collisions or core-collapse supernovae. In astrophysical applications, the excluded volume concept is commonly used for the description of light clusters. Here we compare a phenomenological excluded volume approach to two quantum many-body models, the quantum statistical model and the generalized relativistic mean field model. All three models contain bound states of nuclei with mass number A <= 4. It is explored to which extent the complex medium effects can be mimicked by the simpler excluded volume model, regarding the chemical composition and thermodynamic variables. Furthermore, the role of heavy nuclei and excited states is investigated by use of the excluded volume model. At temperatures of a few MeV the excluded volume model gives a poor description of the medium effects on the light clusters, but there the composition is actually dominated by heavy nuclei. At larger temperatures there is a rather good agreement, whereas some smaller differences and model dependencies remain.

  7. Inflammatory bowel disease and leukemia

    Microsoft Academic Search

    Seid Hossein Mir Madjlessi; Richard G. Farmer; James K. Weick

    1986-01-01

    In a review of a large number of patients with inflammatory bowel disease, leukemia was observed in five patients with chronic ulcerative colitis and in two patients with Crohn's disease. In ulcerative colitis patients, there were three cases of acute myelocytic leukemia and one case each of acute lymphoblastic leukemia and chronic granulocytic leukemia. In Crohn's disease patients, there was

  8. Update on pediatric leukemia and lymphoma imaging.

    PubMed

    Averill, Lauren W; Acikgoz, Gunsel; Miller, Robin E; Kandula, Vinay V R; Epelman, Monica

    2013-12-01

    Together, leukemia and lymphoma account for half of all childhood malignancies. Leukemia and lymphoma arise from similar cell lines and can have overlapping imaging features; however, the clinical presentation, imaging strategies, and treatment protocols can vary substantially based on the specific subtype. Although imaging does not play a central role in staging or monitoring disease in childhood leukemia, findings on imaging may be the first indication of the diagnosis. Advanced imaging, especially positron emission tomography/computed tomography, has moved to the forefront of staging and treatment response evaluation in Hodgkin's disease and non-Hodgkin's lymphoma. Imaging also plays a key role in evaluating the myriad of treatment complications that are commonly seen with chemotherapy and associated neutropenia. Future efforts will be largely focused on decreasing radiation exposure to these children, utilizing reduced or radiation-free modalities, such as positron emission tomography/magnetic resonance and diffusion-weighted whole-body imaging with background suppression, as well as refining surveillance imaging strategies. The purpose of this article is to briefly review the classification of pediatric leukemia and lymphoma, illustrate common imaging findings at presentation throughout the body, describe staging and therapeutic response evaluation, and show a spectrum of commonly encountered complications of treatment. PMID:24332209

  9. How Is Acute Lymphocytic Leukemia Found?

    MedlinePLUS

    ... How is acute lymphocytic leukemia classified? How is acute lymphocytic leukemia found? At this time there are no special ... oncologist (doctor who treats cancer). Tests to find acute lymphocytic leukemia Most of the symptoms seen in leukemia can ...

  10. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePLUS

    ... document focuses on acute lymphocytic leukemia (ALL) in adults. For information on ALL in children, please see ... Leukemia . Chronic leukemias and acute myeloid leukemia of adults are discussed in other American Cancer Society documents. ...

  11. Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-16

    B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  12. Mitoxantrone resistance in HL-60 leukemia cells: Reduced nuclear topoisomerase II catalytic activity and drug-induced DNA cleavage in association with reduced expression of the topoisomerase II. beta. isoform

    SciTech Connect

    Harker, W.G.; Slade, D.L.; Parr, R.L. (Univ. of Utah, Salt Lake City (United States)); Drake, F.H. (SmithKline Beecham Pharmaceuticals, King of Prussia, PA (United States))

    1991-10-15

    Mitoxantrone-resistant variants of the human HL-60 leukemia cell line are cross-resistant to several natural product and synthetic antineoplastic agents. The resistant cells (HL-60/MX2) retain sensitivity to the Vinca alkaloids vincristine and vinblastine, drugs that are typically associated with the classical multidrug resistance phenotype. Mitoxantrone accumulation and retention are equivalent in the sensitive and resistant cell types, suggesting that mitoxantrone resistance inn HL-60/MX2 cells might be associated with an alteration in the type II DNA topoisomerases. The authors discovered that topoisomerase II catalytic activity in 1.0 M NaCl nuclear extracts from the HL-60/MX2 variant was reduced 4- to 5-fold compared to that in the parental HL-60 cells. Studies were designed to minimize the proteolytic degradation of the topoisomerase II enzymes by extraction of whole cells with hot SDS. When nuclear extracts from the two cell types were normalized for equivalent catalytic activity, mitoxantrone inhibited the decatenation of kDNA by these extracts to an equal extent but levels of mitoxantrone-induced cleavage of {sup 32}P-labeled pBR322 DNA by nuclear extracts from HL-60/MX2 cells were 3- to 4-fold lower than in comparable HL-60 extracts. Resistance to the topoisomerase II inhibitor mitoxantrone in HL-60/MX2 is associated with reduced nuclear and whole cell topoisomerase II catalytic activity, immunologically undetectable levels of the 180-kDa topoisomerase II isozyme, and reduced mitoxantrone-induced cleavage of radiolabeled DNA by topoisomerase II in nuclear extracts from these cells.

  13. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  14. Leukemia & Lymphoma Society

    MedlinePLUS

    ... daily chemotherapy that followed his diagnosis with acute lymphoblastic leukemia. Though his treatments continue (3-1/2 years in total), ... Lymphoma Survivor The Woodlands, TX I was diagnosed with ...

  15. Large Granular Lymphocytic Leukemia

    MedlinePLUS

    ... daily chemotherapy that followed his diagnosis with acute lymphoblastic leukemia. Though his treatments continue (3-1/2 years in total), ... Lymphoma Survivor The Woodlands, TX I was diagnosed with ...

  16. Acute Lymphoblastic Leukemia | Office of Cancer Genomics

    Cancer.gov

    Acute lymphoblastic leukemia (ALL) is a cancer of white blood cells, the cells in the body that normally fight infection. It is the most common cancer in children. Over the last several decades, advances in the treatment and supportive care of pediatric ALL have dramatically increased its 5-year survival rate to almost 90%. Despite these improvements, a considerable number of children with ALL continue to relapse following standardized treatment.

  17. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Reuters -June 19, 2008 Approach enlists immune system to fight leukemia

    E-print Network

    Levy, Doron

    Reuters - June 19, 2008 Approach enlists immune system to fight leukemia Leukemia patients may said. The idea behind the new approach is to get the body's own immune system to take over the fight diagnosed, the immune system of CML patients is low, but as they begin to respond to treatment, the immune

  19. Thrombosis and acute leukemia.

    PubMed

    Crespo-Solís, Erick

    2012-04-01

    Thrombosis is a common complication in patients with acute leukemia. While the presence of central venous lines, concomitant steroids, the use of Escherichia coli asparaginase and hereditary thrombophilic abnormalities are known risk factors for thrombosis in children, information on the pathogenesis, risk factors, and clinical outcome of thrombosis in adult patients with acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is still scarce. Expert consensus and guidelines regarding leukemia-specific risk factors, thrombosis prevention, and treatment strategies, as well as optimal type of central venous catheter in acute leukemia patients are required. It is likely that each subtype of acute leukemia represents a different setting for the development of thrombosis and the risk of bleeding. This is perhaps due to a combination of different disease-specific pathogenic mechanisms of thrombosis, including the type of chemotherapy protocol chosen, the underlying patients health, associated risk factors, as well as the biology of the disease itself. The risk of thrombosis may also vary according to ethnicity and prevalence of hereditary risk factors for thrombosis; thus, it is advisable for Latin American, Asian, and African countries to report on their specific patient population. PMID:22507812

  20. Genes and childhood leukemia.

    PubMed

    K?sy, Julita; Januszkiewicz-Lewandowska, Danuta

    2015-01-01

    Leukemia is a heterogeneous hematologic malignancy originating from a multipotent hematopoietic stem cell. It ranks among the commonest cancers in childhood and is characterized by excessive proliferation and differentiation block. The process of leukemogenesis is governed by genetic changes at both the cytogenetic and molecular level. According to numerous analyses, a large spectrum of mutations and rearrangements underlying the disease affect essential cellular transduction pathways, genes ensuring proper course of hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators. Common lesions include translocations to T cell receptor (TCR) loci in T-lineage acute lymphoblastic leukemia (T-ALL), mutations of transcription factors regulating B-lineage development and cell maturation in B-lineage acute lymphoblastic leukemia (B-ALL) (PAX5, TCF3, EBF1, etc.), aberrational disruption of genes coding for transcription factors and coactivators in acute myeloid leukemia (AML) (e.g. CBF) or BCR-ABL1 fusion and activation of multiple kinases in chronic myeloid leukemia (CML). These alterations severely impair cell function. Broadening knowledge of the genetic background gives an insight into the pathobiology of a disease and allows for a better understanding of it. An appropriate investigation of genomic events yields diagnostic, prognostic and therapeutic implications. Broadening knowledge of the pathogenesis of leukemia seems to be a promising contribution to precise stratification of patients, reducing the toxicity and adverse effects caused by medical intervention, treatment personalization and introduction of targeted therapy accessible to a wide range of patients. PMID:25748621

  1. The Chernobyl Accident: Leukemia Study (Ukraine)

    Cancer.gov

    Several years after a 1988 agreement between the United States and the USSR to cooperate in the area of nuclear reactor safety, the National Cancer Institute (NCI), NIH undertook to develop a study of leukemia risk among Ukrainian men potentially exposed to external radiation during clean-up operations (e.g., liquidators) following the Chernobyl accident. Responsibility for the study resides in the Radiation Epidemiology Branch of NCI.

  2. Bromodomain and extraterminal (BET) protein inhibition suppresses human T cell leukemia virus 1 (HTLV-1) Tax protein-mediated tumorigenesis by inhibiting nuclear factor ?B (NF-?B) signaling.

    PubMed

    Wu, Xuewei; Qi, Jun; Bradner, James E; Xiao, Gutian; Chen, Lin-Feng

    2013-12-13

    The etiology of human T cell leukemia virus 1 (HTLV-1)-mediated adult T cell leukemia is associated with the ability of viral oncoprotein Tax to induce sustained NF-?B activation and the expression of many NF-?B target genes. Acetylation of the RelA subunit of NF-?B and the subsequent recruitment of bromodomain-containing factor Brd4 are important for the expression of NF-?B target genes in response to various stimuli. However, their contributions to Tax-mediated NF-?B target gene expression and tumorigenesis remain unclear. Here we report that Tax induced the acetylation of lysine 310 of RelA and the binding of Brd4 to acetylated RelA to facilitate Tax-mediated transcriptional activation of NF-?B. Depletion of Brd4 down-regulated Tax-mediated NF-?B target gene expression and cell proliferation. Inhibiting the interaction of Brd4 and acetylated RelA with the bromodomain extraterminal protein inhibitor JQ1 suppressed the proliferation of Tax-expressing rat fibroblasts and Tax-positive HTLV-1-infected cells and Tax-mediated cell transformation and tumorigenesis. Moreover, JQ1 attenuated the Tax-mediated transcriptional activation of NF-?B, triggering the polyubiquitination and proteasome-mediated degradation of constitutively active nuclear RelA. Our results identify Brd4 as a key regulator for Tax-mediated NF-?B gene expression and suggest that targeting epigenetic regulators such as Brd4 with the bromodomain extraterminal protein inhibitor might be a potential therapeutic strategy for cancers and other diseases associated with HTLV-1 infection. PMID:24189064

  3. Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product.

    PubMed

    Wilkinson, G W; Kelly, C; Sinclair, J H; Rickards, C

    1998-05-01

    The PML gene product is associated with a defined nuclear structure (10-20 per cell) known variously as PML-bodies, ND10, PODs or Kr bodies. Certain conditions are known to compromise the integrity of PML-bodies; these include environmental stress (e.g. heat shock), a chromosomal translocation-associated acute promyelocytic leukaemia, and infection with certain viruses [including human cytomegalovirus (HCMV), herpes simplex virus type 1 and adenovirus]. Expression of the HCMV major immediate early (IE) protein (IE1(491aa)) is by itself sufficient to cause disruption of PML-bodies, resulting in the dispersal of the PML antigen uniformly throughout the nucleus. In uninfected cells undergoing mitosis PML is excluded from chromatin. However, both IE1(491aa) and PML were observed to associate with mitotic chromosomes in cells infected with HCMV or transfected with the IE1 gene. A series of in-frame IE1 deletion mutants was used in DNA transfection experiments to identify two large sequence elements (aa 132-274 and the C-terminal aa 347-491) not required for dispersal of the PML antigen. However, a putative leucine-zipper domain (aa 105-139), a putative zinc-finger domain (aa 267-286) and exon 2 and 3 coding sequences (aa 6-85) were required. The association of the IE1 gene product with chromatin required an acidic domain near the C terminus (aa 421-486). The interaction of IE1(491aa) with chromatin was therefore not required for the disruption of PML-bodies. Exon 2 (aa 1-24) was shown to encode a nuclear localization signal. PMID:9603339

  4. Requirement of the spindle pole body for targeting and/or tethering proteins to the inner nuclear membrane.

    PubMed

    Diaz-Muñoz, Greetchen; Harchar, Terri A; Lai, Tsung-Po; Shen, Kuo-Fang; Hopper, Anita K

    2014-01-01

    Appropriate targeting of inner nuclear membrane (INM) proteins is important for nuclear function and architecture. To gain new insights into the mechanism(s) for targeting and/or tethering peripherally associated proteins to the INM, we screened a collection of temperature sensitive S. cerevisiae yeast mutants for defects in INM location of the peripheral protein, Trm1-II-GFP. We uncovered numerous genes encoding components of the Spindle Pole Body (SPB), the yeast centrosome. SPB alterations affect the localization of both an integral (Heh2) and a peripheral INM protein (Trm1-II-GFP), but not a nucleoplasmic protein (Pus1). In wild-type cells Trm1-II-GFP is evenly distributed around the INM, but in SPB mutants, Trm1-II-GFP mislocalizes as a spot(s) near ER-nucleus junctions, perhaps its initial contact site with the nuclear envelope. Employing live cell imaging over time in a microfluidic perfusion system to study protein dynamics, we show that both Trm1-II-GFP INM targeting and maintenance depend upon the SPB. We propose a novel targeting and/or tethering model for a peripherally associated INM protein that combines mechanisms of both integral and soluble nuclear proteins, and describe a role of the SPB in nuclear envelope dynamics that affects this process. PMID:25482124

  5. Requirement of the spindle pole body for targeting and/or tethering proteins to the inner nuclear membrane

    PubMed Central

    Diaz-Muñoz, Greetchen; Harchar, Terri A; Lai, Tsung-Po; Shen, Kuo-Fang; Hopper, Anita K

    2014-01-01

    Appropriate targeting of inner nuclear membrane (INM) proteins is important for nuclear function and architecture. To gain new insights into the mechanism(s) for targeting and/or tethering peripherally associated proteins to the INM, we screened a collection of temperature sensitive S. cerevisiae yeast mutants for defects in INM location of the peripheral protein, Trm1-II-GFP. We uncovered numerous genes encoding components of the Spindle Pole Body (SPB), the yeast centrosome. SPB alterations affect the localization of both an integral (Heh2) and a peripheral INM protein (Trm1-II-GFP), but not a nucleoplasmic protein (Pus1). In wild-type cells Trm1-II-GFP is evenly distributed around the INM, but in SPB mutants, Trm1-II-GFP mislocalizes as a spot(s) near ER-nucleus junctions, perhaps its initial contact site with the nuclear envelope. Employing live cell imaging over time in a microfluidic perfusion system to study protein dynamics, we show that both Trm1-II-GFP INM targeting and maintenance depend upon the SPB. We propose a novel targeting and/or tethering model for a peripherally associated INM protein that combines mechanisms of both integral and soluble nuclear proteins, and describe a role of the SPB in nuclear envelope dynamics that affects this process. PMID:25482124

  6. HIV, leukemia, and new horizons in molecular therapy.

    PubMed

    Berkhout, Ben

    2013-08-01

    Cancer and human immunodeficiency virus (HIV) are both scary things to have in your body, but a new treatment is successfully using the latter against the former. Recent news reports, among others in the New York Times, talked about this new cure for leukemia by using HIV. This mini-review puts this news in perspective and provides a broader view as there appear to be several areas where clinical research on HIV and leukemia seem to connect. The topics covered range from antiviral gene therapy approaches using HIV-based lentiviral vectors to the risk of leukemia induction by these integrating vectors, and from an anti-leukemia transplantation strategy that turned out to provide a functional cure for HIV, to novel vaccination approaches. PMID:24016608

  7. Is obesity a prognostic factor for acute myeloid leukemia outcome?

    PubMed Central

    Lee, Hun Ju; Licht, Andrea S.; Hyland, Andrew J.; Ford, Laurie A.; Sait, Sheila N. J.; Block, AnneMarie W.; Barcos, Maurice; Baer, Maria R.; Wang, Eunice S.

    2015-01-01

    Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity, measured by body mass index (BMI), affected outcome in 329 adult AML patients treated with high-dose cytarabine and idarubicin-containing regimens administered according to actual body weight. Age?60, unfavorable karyotype, secondary AML, and positive smoking status had adverse impact on overall survival in a multivariate analysis, while BMI did not. We conclude that high BMI should not be a barrier to administer high-dose cytarabine-containing regimens for AML induction. PMID:21935651

  8. What Is Chronic Lymphocytic Leukemia?

    MedlinePLUS

    ... of this document focuses mainly on CLL in adults, with some limited information on hairy cell leukemia. For information on other types of leukemia in adults and children, please see our separate documents on ...

  9. Double Decimation and Sliding Vacua in the Nuclear Many-Body System

    E-print Network

    Brown, G E; Rho, Mannque

    2004-01-01

    We propose that effective field theories for nuclei and nuclear matter comprise of "double decimation": (1) the chiral symmetry decimation (CSD) and (2) Fermi liquid decimation (FLD). The Brown-Rho scaling recently identified as the parametric dependence intrinsic in the "vector manifestation" of hidden local symmetry theory of Harada and Yamawaki results from the first decimation. This scaling governs dynamics down to the scale at which the Fermi surface is formed as a quantum critical phenomenon. The next decimation to the top of the Fermi sea where standard nuclear physics is operative makes up the Fermi liquid decimation. Thus nuclear dynamics is dictated by two fixed points, namely, the vector manifestation fixed point and the Fermi liquid fixed point. It has been a prevalent practice in nuclear physics community to proceed with the second decimation only, assuming density independent masses. We show why most nuclear phenomena can be reproduced by theories using either density-independent, or density-dep...

  10. Investigation of anti-leukemia molecular mechanism of ITR-284, a carboxamide analog, in leukemia cells and its effects in WEHI-3 leukemia mice.

    PubMed

    Wen, Yen-Fang; Yang, Jai-Sing; Kuo, Sheng-Chu; Hwang, Chrong-Shiong; Chung, Jing-Gung; Wu, Hsi-Chin; Huang, Wen-Wen; Jhan, Jia-Hua; Lin, Chung-Ming; Chen, Hui-Jye

    2010-02-01

    ITR-284, a potent anti-leukemia agent of carboxamide derivative, has been shown to inhibit the proliferation of leukemia cells. In this study, the underlying molecular mechanisms in vitro and anti-leukemia activity in vivo of ITR-284 were investigated. ITR-284 reduced the cell viability and induced apoptosis in HL-60 and WEHI-3 leukemia cells. Following exposure of cells to 30 nM of ITR-284, there is a time-dependent decrease in the mitochondrial membrane potential (DeltaPsi(m)) and an increase in the reactive oxygen species (ROS). ITR-284 treatment also caused a time-dependent increase of Fas/CD95, cytosolic cytochrome c, cytosolic active form of caspase-8/-9/-3, cytosolic Apaf-1 and Bax, and the decrease of Bcl-2. However, the ITR-284-induced caspase-8/-9 and -3 activities can be blocked by pan-caspase inhibitor (Z-VAD-FMK). In addition, the anti-leukemia effects of ITR-284 in vivo were further evaluated in BALB/c mice inoculated with WEHI-3 cells. Orally treatment with ITR-284 (2 and 10mg/kg/alternate day for 7 times) increased the survival rate and prevented the loss of body weight in leukemia mice. The enlargement of spleen and infiltration of immature myeloblastic cells into spleen red pulp were significantly reduced in ITR-284-treated mice compared with control mice. Moreover, ITR-284 application can enhance the anti-leukemia effect of all-trans retinoic acid (ATRA). These results revealed that ITR-284 acted against both HL-60 and WEHI-3 in vitrovia both intrinsic and extrinsic apoptotic signaling pathways, and exhibited an anti-leukemic effect in a WEHI-3 orthotopic mice model of leukemia. PMID:19765549

  11. Connecting neutron star observations to three-body forces in neutron matter and to the nuclear symmetry energy.

    PubMed

    Steiner, A W; Gandolfi, S

    2012-02-24

    Using a phenomenological form of the equation of state of neutron matter near the saturation density which has been previously demonstrated to be a good characterization of quantum Monte Carlo simulations, we show that currently available neutron star mass and radius measurements provide a significant constraint on the equation of state of neutron matter. At higher densities we model the equation of state by using polytropes and a quark matter model. We show that observations offer an important constraint on the strength of the three-body force in neutron matter, and thus some theoretical models of the three-body force may be ruled out by currently available astrophysical data. In addition, we obtain an estimate of the symmetry energy of nuclear matter and its slope that can be directly compared to the experiment and other theoretical calculations. PMID:22463511

  12. ACUTE LYMPHOBLASTIC LEUKEMIA FALLON, NEVADA

    E-print Network

    1 ACUTE LYMPHOBLASTIC LEUKEMIA FALLON, NEVADA REVIEW AND RECOMMENDATIONS OF THE EXPERT PANEL the state health department's investigation of acute lymphoblastic leukemia (ALL) cases that had been of a hazardous chemical contaminant. However, the absence of cases of acute myeloid leukemia, the type

  13. Nuclear Export Receptor Xpo1/Crm1 Is Physically and Functionally Linked to the Spindle Pole Body in Budding Yeast? †

    PubMed Central

    Neuber, Anja; Franke, Jacqueline; Wittstruck, Angelika; Schlenstedt, Gabriel; Sommer, Thomas; Stade, Katrin

    2008-01-01

    The spindle pole body (SPB) represents the microtubule organizing center in the budding yeast Saccharomyces cerevisiae. It is a highly structured organelle embedded in the nuclear membrane, which is required to anchor microtubules on both sides of the nuclear envelope. The protein Spc72, a component of the SPB, is located at the cytoplasmic face of this organelle and serves as a receptor for the ?-tubulin complex. In this paper we show that it is also a binding partner of the nuclear export receptor Xpo1/Crm1. Xpo1 binds its cargoes in a Ran-dependent fashion via a short leucine-rich nuclear export signal (NES). We show that binding of Spc72 to Xpo1 depends on Ran-GTP and a functional NES in Spc72. Mutations in this NES have severe consequences for mitotic spindle morphology in vivo. This is also the case for xpo1 mutants, which show a reduction in cytoplasmic microtubules. In addition, we find a subpopulation of Xpo1 localized at the SPB. Based on these data, we propose a functional link between Xpo1 and the SPB and discuss a role for this exportin in spindle biogenesis in budding yeast. PMID:18573877

  14. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  15. Leukemia diagnostics with ow G. Ciuperca1

    E-print Network

    Louvet, Violaine

    Leukemia diagnostics with ow cytometry G. Ciuperca1 , M. Mafouz1 , C. Dumontet2 , V. Louvet1 , A'exposé Hematopoiesis and leukemias Flow cytometry Leukemias classication and Medical diagnosis Mathematical Models for diagnosis and classication of acute myeloid leukemia #12;Leukemia diagnostics with ow cytometry G. Ciuperca

  16. Iso-Vectorial interaction and many-body correlations in Nuclear Dynamics

    NASA Astrophysics Data System (ADS)

    Papa, M.

    2014-05-01

    Comparisons involving Nuclear Matter calculations based on the Constraint Molecular model CoMD and semi-classical Mean-Field approximation using an effective interactions of the Skyrme type are presented. The performed study shows that specific correlations induced by the iso-vectorial interaction investigated in the framework of the molecular dynamics approach strongly affect parameter values of the effective interaction to be used to reproduce the standard saturation properties of Nuclear Matter. Moreover an example showing consequences in the balance between reaction mechanisms in the 48Ca +48Ca at 25 MeV/nucleon system is also discussed.

  17. Predictions of Leukemia Risks to Astronauts from Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Cucinotta, F. A.; Atwell, W.; Kim, M. Y.; George, K. A.; Ponomarev, A.; Nikjoo, H.; Wilson, J. W.

    2006-01-01

    Leukemias consisting of acute and chronic myeloid leukemia and acute lymphatic lymphomas represent the earliest cancers that appear after radiation exposure, have a high lethality fraction, and make up a significant fraction of the overall fatal cancer risk from radiation for adults. Several considerations impact the recommendation of a preferred model for the estimation of leukemia risks from solar particle events (SPE's): The BEIR VII report recommends several changes to the method of calculation of leukemia risk compared to the methods recommended by the NCRP Report No. 132 including the preference of a mixture model with additive and multiplicative components in BEIR VII compared to the additive transfer model recommended by NCRP Report No. 132. Proton fluences and doses vary considerably across marrow regions because of the characteristic spectra of primary solar protons making the use of an average dose suspect. Previous estimates of bone marrow doses from SPE's have used an average body-shielding distribution for marrow based on the computerized anatomical man model (CAM). We have developed an 82-point body-shielding distribution that faithfully reproduces the mean and variance of SPE doses in the active marrow regions (head and neck, chest, abdomen, pelvis and thighs) allowing for more accurate estimation of linear- and quadratic-dose components of the marrow response. SPE's have differential dose-rates and a pseudo-quadratic dose response term is possible in the peak-flux period of an event. Also, the mechanistic basis for leukemia risk continues to improve allowing for improved strategies in choosing dose-rate modulation factors and radiation quality descriptors. We make comparisons of the various choices of the components in leukemia risk estimates in formulating our preferred model. A major finding is that leukemia could be the dominant risk to astronauts for a major solar particle event.

  18. Double Decimation and Sliding Vacua in the Nuclear Many-Body System

    E-print Network

    G. E. Brown; Mannque Rho

    2003-05-29

    We propose that effective field theories for nuclei and nuclear matter comprise of "double decimation": (1) the chiral symmetry decimation (CSD) and (2) Fermi liquid decimation (FLD). The Brown-Rho scaling recently identified as the parametric dependence intrinsic in the "vector manifestation" of hidden local symmetry theory of Harada and Yamawaki results from the first decimation. This scaling governs dynamics down to the scale at which the Fermi surface is formed as a quantum critical phenomenon. The next decimation to the top of the Fermi sea where standard nuclear physics is operative makes up the Fermi liquid decimation. Thus nuclear dynamics is dictated by two fixed points, namely, the vector manifestation fixed point and the Fermi liquid fixed point. It has been a prevalent practice in nuclear physics community to proceed with the second decimation only, assuming density independent masses. We show why most nuclear phenomena can be reproduced by theories using either density-independent, or density-dependent masses, a grand conspiracy of nature that is an aspect that could be tied to the Cheshire-Cat phenomenon in hadron physics. We identify what is left out in the Fermi liquid decimation that does not incorporate the CSD. Experiments such as the dilepton production in relativistic heavy ion reactions, which are specifically designed to observe effects of dropping masses, could exhibit large effects from the reduced masses. However they are compounded with effects that are not directly tied to chiral symmetry. We discuss a recent STAR/RHIC observation where BR scaling can be singled out in a pristine environment.

  19. -Arrestin2 mediates the initiation and progression of myeloid leukemia

    E-print Network

    -Arrestin2 mediates the initiation and progression of myeloid leukemia Mark Fereshteha leukemia (CML). These defects are linked to a re- duced frequency, as well as defective self maintenance. chronic myeloid leukemia | leukemia stem cell | hematopoiesis Chronic myelogenous leukemia (CML

  20. Leukemia and Benzene

    PubMed Central

    Snyder, Robert

    2012-01-01

    Excessive exposure to benzene has been known for more than a century to damage the bone marrow resulting in decreases in the numbers of circulating blood cells, and ultimately, aplastic anemia. Of more recent vintage has been the appreciation that an alternative outcome of benzene exposure has been the development of one or more types of leukemia. While many investigators agree that the array of toxic metabolites, generated in the liver or in the bone marrow, can lead to traumatic bone marrow injury, the more subtle mechanisms leading to leukemia have yet to be critically dissected. This problem appears to have more general interest because of the recognition that so-called “second cancer” that results from prior treatment with alkylating agents to yield tumor remissions, often results in a type of leukemia reminiscent of benzene-induced leukemia. Furthermore, there is a growing literature attempting to characterize the fine structure of the marrow and the identification of so called “niches” that house a variety of stem cells and other types of cells. Some of these “niches” may harbor cells capable of initiating leukemias. The control of stem cell differentiation and proliferation via both inter- and intra-cellular signaling will ultimately determine the fate of these transformed stem cells. The ability of these cells to avoid checkpoints that would prevent them from contributing to the leukemogenic response is an additional area for study. Much of the study of benzene-induced bone marrow damage has concentrated on determining which of the benzene metabolites lead to leukemogenesis. The emphasis now should be directed to understanding how benzene metabolites alter bone marrow cell biology. PMID:23066403

  1. Nuf2, a spindle pole body-associated protein required for nuclear division in yeast

    Microsoft Academic Search

    Mark A. Osborne; Gabriel Schlenstedt; Timothy Jinks; Pamela A. Silver

    1994-01-01

    The NUF2 gene of the yeast Saccharomyces cerevisiae encodes an essential 53-kd protein with a high content of potential coiled-coil structure similar to myosin. Nuf2 is associated with the spindle pole body (SPB) as determined by coimmunofluorescence with known SPB proteins. Nuf2 appears to be local- ized to the intranuclear region and is a candidate for a protein involved in

  2. On classical hydrodynamics and collective motion as approximation to the nuclear many-body problem

    Microsoft Academic Search

    Hans-Christian Pauli

    1980-01-01

    Using time-dependent unitary transformations, one can cast a one-body equation of the time-dependent Hartree-Fock type into a form which is closely related to equations for a classical irrotational fluid. The hydrodynamic equation of state finds its counterpart in a stationary constrained field equation. The hydrodynamic equations in turn can be translated into a classical Hamiltonian formalism with an infinite number

  3. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2014-08-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  4. Juvenile Myelomonocytic Leukemia (JMML) (For Parents)

    MedlinePLUS

    ... Kids Safe Concussions: What to Know Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > Parents > Diseases & Conditions > Cancer & Tumors > Juvenile ... Causes Signs and Symptoms Diagnosis Treatment Coping About Leukemia Leukemia is a type of cancer that affects ...

  5. Genetics Home Reference: Acute promyelocytic leukemia

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Acute promyelocytic leukemia On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed April 2011 What is acute promyelocytic leukemia? Acute promyelocytic leukemia is a form of acute ...

  6. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    ClinicalTrials.gov

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  7. for Bone Marrow Purging in Acute Lymphoid Leukemia

    Microsoft Academic Search

    Dario Campana; George Janossy

    2010-01-01

    In this paper a microplate method is described for diagnos- ing acute leukemia and for investigating the reactivity of monoclonal antibodies (MoAbs) against membrane anti- gens in combination with rabbit or munine antibodies to nuclear terminal transferase (TdT). The speed of this method facilitates the investigation of fresh leukemic cells from individual patients and assesses the cytolytic efficacy of the

  8. Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Relapsing Chronic Myelogenous Leukemia

  9. Electron tomography of fiber cell cytoplasm and dense cores of multilamellar bodies from human age-related nuclear cataracts

    PubMed Central

    Costello, M. Joseph; Burette, Alain; Weber, Mariko; Metlapally, Sangeetha; Gilliland, Kurt O.; Fowler, W. Craig; Mohamed, Ashik; Johnsen, Sönke

    2012-01-01

    Human nuclear cataract formation is a multi-factorial disease with contributions to light scattering from many cellular sources that change their scattering properties over decades. The aging process produces aggregation of cytoplasmic crystallin proteins, which alters the protein packing and texture of the cytoplasm. Previous studies of the cytoplasmic texture quantified increases in density fluctuations in protein packing and theoretically predicted the corresponding scattering. Multilamellar bodies (MLBs) are large particles with a core of crystallin cytoplasm that have been suggested to be major sources of scattering in human nuclei. The core has been shown to condense over time such that the refractive index increases compared to the adjacent aged and textured cytoplasm. Electron tomography is used here to visualize the 3D arrangement of protein aggregates in aged and cataractous lens nuclear cytoplasm compared to the dense protein packing in the cores of MLBs. Thin sections, 70 nm thick, were prepared from epoxy-embedded human transparent donor lenses and nuclear cataracts. Tilt series were collected on an FEI T20 transmission electron microscope (TEM) operated at 200 kV using 15 nm gold particles as fiducial markers. Images were aligned and corrected with FEI software and reconstructed with IMOD and other software packages to produce animated tilt series and stereo anaglyphs. The 3D views of protein density showed the relatively uniform packing of proteins in aged transparent lens nuclear cytoplasm and less dense packing of aged cataractous cytoplasm where many low-density regions can be appreciated in the absence of the TEM projection artifacts. In contrast the cores of the MLBs showed a dense packing of protein with minimal density fluctuations. These observations support the conclusion that, during the nuclear cataract formation, alterations in protein packing are extensive and can result in pronounced density fluctuations. Aging causes the MLB cores to become increasingly different in their protein packing from the adjacent cytoplasm. These results support the hypothesis that the MLBs increase their scattering with age and nuclear cataract formation. PMID:22728317

  10. Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

    ClinicalTrials.gov

    2009-01-29

    Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

  11. Studies of a nuclear matrix protein restricted to normal brain cells and lead-induced intranuclear inclusion bodies of kidney

    SciTech Connect

    Shelton, K.; Egle, P.; Redford, K.; Bigbee, J.

    1986-05-01

    A nuclear matrix protein, p32/6.3, with an unusual tissue distribution, has been identified. Protein from 21 tissues was surveyed by immunoprobing Western blots. In normal adult rats p32/6.3 is found only in grey matter from the cerebrum and the cerebellum, occurring in both neurons and astrocytes. Other brain cell types have not been examined. The protein appears to be developmentally regulated. It is detectable in the brain within a few days after birth and reaches adult levels within one to two weeks. Brain p32/6.3 has been found in all animals tested including rat, mouse, dog, cow, pig, chicken and human. This conservation indicates a fundamental role for p32/6.3 in the nucleus of brain cells. Possible functions for p32/6.3 may be indicated by a second novel occurrence. Chronic lead poisoning characteristically induces intranuclear inclusion bodies in the cells lining kidney proximal tubules. p32/6.3 is a major constituent of these inclusion bodies. They are also rich in lead and other metals including calcium, iron, zinc, copper and cadmium. These diverse observations suggest that p32/6.3 may have a role in metal homeostasis in the brain of normal animals.

  12. Yields of Soviet underground nuclear explosions at Novaya Zemlya, 1964-1976, from seismic body and surface waves

    SciTech Connect

    Sykes, L.R.; Wiggins, G.C.

    1986-01-01

    Surface and body wave magnitudes are determined for 15 USSR underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (m/sub b/) values indicates a clustering of explosions at a few specific yields. The most pronounced cluster consists of six explosions of yield near 500 kilotons. Several of these seem to be tests of warheads for major strategic systems that became operational in the late 1970s. The largest Soviet underground explosion is estimated to have a yield of 3500 +/- 600 kilotons, somewhat smaller than the yield of the largest US underground test. A preliminary estimation of the significance of tectonic release is made by measuring the amplitude of Love waves. The bias in m/sub b/ for Novaya Zemlya relative to the Nevada test site is about 0.35, nearly identical to that of the eastern Kazakhstan test site relative to Nevada.

  13. Yields of Soviet underground nuclear explosions at Novaya Zemlya, 1964-1976, from seismic body and surface waves

    PubMed Central

    Sykes, Lynn R.; Wiggins, Graham C.

    1986-01-01

    Surface and body wave magnitudes are determined for 15 U.S.S.R. underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (mb) values indicates a clustering of explosions at a few specific yields. The most pronounced cluster consists of six explosions of yield near 500 kilotons. Several of these seem to be tests of warheads for major strategic systems that became operational in the late 1970s. The largest Soviet underground explosion is estimated to have a yield of 3500 ± 600 kilotons, somewhat smaller than the yield of the largest U.S. underground test. A preliminary estimation of the significance of tectonic release is made by measuring the amplitude of Love waves. The bias in mb for Novaya Zemlya relative to the Nevada test site is about 0.35, nearly identical to that of the eastern Kazakhstan test site relative to Nevada. PMID:16593645

  14. Yields of Soviet underground nuclear explosions at Novaya Zemlya, 1964-1976, from seismic body and surface waves.

    PubMed

    Sykes, L R; Wiggins, G C

    1986-01-01

    Surface and body wave magnitudes are determined for 15 U.S.S.R. underground nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are used to estimate yields. These events include the largest underground explosions detonated by the Soviet Union. A histogram of body wave magnitude (m(b)) values indicates a clustering of explosions at a few specific yields. The most pronounced cluster consists of six explosions of yield near 500 kilotons. Several of these seem to be tests of warheads for major strategic systems that became operational in the late 1970s. The largest Soviet underground explosion is estimated to have a yield of 3500 +/- 600 kilotons, somewhat smaller than the yield of the largest U.S. underground test. A preliminary estimation of the significance of tectonic release is made by measuring the amplitude of Love waves. The bias in m(b) for Novaya Zemlya relative to the Nevada test site is about 0.35, nearly identical to that of the eastern Kazakhstan test site relative to Nevada. PMID:16593645

  15. High Precision Three-body Variational Method for Critical Nuclear Charge

    NASA Astrophysics Data System (ADS)

    Busuttil, Michael A.

    For an atom there exists a critical nuclear charge Zc that is just sufficient to bind the nucleus and its electrons into a stable configuration. A study of the critical charge for two-electron atoms is presented with the purpose of improving accuracy for Zc. To this end, high precision techniques involving the variational method with multiple basis sets in Hylleraas coordinates are employed. The method is particularly well adapted to the case where one electron is strongly bound and the other is at the limit of becoming unbound. The results are analysed in terms of fractional powers of (Z -- Zc) related to the analytic structure of the energy E( Z) and a 1/Z expansion for the energy. This results in a Zc of 0.91102808(5). Future work prompted by this study includes development of direct techniques to determine Zc utilizing the low-Z stability of the method; developing the framework and mathematical justification for a novel bootstrap analysis method used in curve-fitting; and investigating the inclusion of finite nuclear mass, relativistic effects, and other higher order corrections in the determination of Zc.

  16. Lymphoblastic Leukemia and Lymphoma

    Microsoft Academic Search

    Andrea M. Sheehan

    \\u000a This chapter covers T and B lymphoblastic neoplasms, including acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma\\u000a (LBL). Morphologic, immunophenotypic, and cytogenetic features are discussed along with the parameters of various modalities\\u000a used in their diagnosis. The techniques and utility of minimum residual disease (MRD) measurement after therapy is discussed,\\u000a as are new insights into the molecular biology of leukemogenesis gleaned

  17. Large granular lymphocyte leukemia

    Microsoft Academic Search

    Lubomir Sokol; Thomas P. Loughran

    2007-01-01

    Clonal diseases of large granular lymphocytes (LGLs) represent a spectrum of clinically rare lymphoproliferative malignancies\\u000a arising from either mature T-cell (CD3+) or natural killer (NK)-cell (CD3?) lineages. The clinical behavior of these disorders ranges from indolent to very aggressive. Patients with symptomatic indolent\\u000a T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies; in contrast, aggressive T-cell or NK-cell

  18. Computational approaches to many-body dynamics of unstable nuclear systems

    E-print Network

    Alexander Volya

    2014-12-19

    The goal of this presentation is to highlight various computational techniques used to study dynamics of quantum many-body systems. We examine the projection and variable phase methods being applied to multi-channel problems of scattering and tunneling; here the virtual, energy-forbidden channels and their treatment are of particular importance. The direct time-dependent solutions using Trotter-Suzuki propagator expansion provide yet another approach to exploring the complex dynamics of unstable systems. While presenting computational tools, we briefly revisit the general theory of the quantum decay of unstable states. The list of questions here includes those of the internal dynamics in decaying systems, formation and evolution of the radiating state, and low-energy background that dominates at remote times. Mathematical formulations and numerical approaches to time-dependent problems are discussed using the quasi-stationary methods involving effective Non-Hermitian Hamiltonian formulation.

  19. Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer.

    PubMed Central

    Zhang, Z. F.; Zeng, Z. S.; Sarkis, A. S.; Klimstra, D. S.; Charytonowicz, E.; Pollack, D.; Vena, J.; Guillem, J.; Marshall, J. R.; Cordon-Cardo, C.

    1995-01-01

    To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%) patients displaying p53-positive phenotype, defined as > or = 25% of positive cells. Patients with two or more first-degree relatives with cancer had an odds ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with those without a family history of cancer (trend test, P = 0.11). A possible association between body weight and p53 overexpression was observed. The ORs were 1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest quartile in comparison with the lowest quartile (trend test, P = 0.06). No association between occupational physical activity, smoking, drinking, parity and p53 overexpression was identified. The results suggest that p53 overexpression may be related to genetic predisposition to colorectal cancer, and p53-positive and p53-negative colorectal cancers may be controlled by different aetiological pathways. Images Figure 1 PMID:7710960

  20. The Canonical Nuclear Many-Body Problem as an Effective Theory

    E-print Network

    W. C. Haxton; T. Luu

    2001-01-22

    Recently it was argued that it might be possible treat the conventional nuclear structure problem -- nonrelativistic point nucleons interacting through a static and rather singular potential -- as an effective theory in a shell-model basis. In the first half of this talk we describe how such a program can be carried out for the simplest nuclei, the deuteron and 3He, exploiting a new numerical technique for solving the self-consistent Bloch-Horowitz equation. Some of the properties of proper effective theories are thus illustrated and contrasted with the shell model. In the second half of the talk we use these examples to return to a problem that frustrated the field three decades ago, the possibility of reducing the effective interactions problem to perturbation theory. We show, by exploiting the Talmi integral expansion, that hard-core potentials can be systematically softened by the introduction of a series of contact operators familiar from effective field theory. The coefficients of these operators can be run analytically by a renormalization group method in a scheme-independent way, with the introduction of suitable counterterms. Once these coefficients are run to the shell model scale, we show that the renormalized coefficients contain all of the information needed to evaluate perturbative insertions of the remaining soft potential. The resulting perturbative expansion is shown to converge in lowest order for the simplest nucleus, the deuteron.

  1. The Canonical Nuclear Many-Body Problem as an Effective Theory

    E-print Network

    Haxton, W C

    2001-01-01

    Recently it was argued that it might be possible treat the conventional nuclear structure problem - nonrelativistic point nucleons interacting through a static and rather singular potential - as an effective theory in a shell-model basis. In the first half of this talk we describe how such a program can be carried out for the simplest nuclei, the deuteron and 3He, exploiting a new numerical technique for solving the self-consistent Bloch-Horowitz equation. Some of the properties of proper effective theories are thus illustrated and contrasted with the shell model. In the second half of the talk we use these examples to return to a problem that frustrated the field three decades ago, the possibility of reducing the effective interactions problem to perturbation theory. We show, by exploiting the Talmi integral expansion, that hard-core potentials can be systematically softened by the introduction of a series of contact operators familiar from effective field theory. The coefficients of these operators can be r...

  2. Developmental Outcome of Childhood Leukemia.

    ERIC Educational Resources Information Center

    Coniglio, Susan J.; Blackman, James A.

    1995-01-01

    Literature on developmental and psychosocial outcomes of childhood leukemia is reviewed, focusing on preschool-age children. Studies are categorized in terms of outcome measures: intelligence/achievement, neuropsychological, memory/attention, and psychosocial tests. Evidence suggests that preschool children with leukemia are at high risk for…

  3. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    ClinicalTrials.gov

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. Resistance to 1,25D-induced differentiation in human acute myeloid leukemia HL60-40AF cells is associated with reduced transcriptional activity and nuclear localization of the vitamin D receptor.

    PubMed

    Garay, Edward; Donnelly, Robert; Wang, Xuening; Studzinski, George P

    2007-12-01

    The anti-neoplastic effects of 1,25-dihydroxyvitamin D3 (1,25D) are well documented in numerous tumor cell systems and animal models of cancer. However, despite this pre-clinical success, the clinical use of 1,25D is currently impeded by the dose-limiting hypercalcemia, and the risk of development of resistance to 1,25D. In this study, we investigated the mechanism of resistance to 1,25D of HL60-40AF cells, a model of drug-resistant acute myeloid leukemia, derived from HL60 cells by cultivation in the presence of 1,25D. The data indicate that transcriptional activity of vitamin D receptor (VDR) in 40AF cells increases only briefly when the cells are treated with 1,25D, despite greater basal cellular levels of VDR protein in the resistant than in the 1,25D-sensitive cells. Analysis of the 40AF VDR mRNA sequence indicated alterations in the 5' untranslated region (UTR), but coding domain variations were not observed. When resistance to 1,25D-induced differentiation of 40AF cells was reversed by a combination of 1,25D with potentiators of differentiation (plant derived antioxidants and a p38MAPK inhibitor), an increase in the level of nuclear VDR, as well as an increase in CYP24 mRNA expression was observed. These data suggest that decreased ability of 1,25D to induce VDR nuclear localization and the consequent VDR target gene transcription may be an important reason for the resistance of 40AF cells to 1,25D. Further, our data show that VDR localization and phosphorylation can be increased by combining 1,25D with potentiators of differentiation. Analysis of the mechanisms that underlie the reduction and potentiation of 1,25D-mediated changes in VDR activity may lead to the identification of new cellular targets that enhance 1,25D-induced monocytic differentiation. PMID:17520689

  5. Resistance to 1,25D-Induced Differentiation in Human Acute Myeloid Leukemia HL60-40AF Cells Is Associated With Reduced Transcriptional Activity and Nuclear Localization of the Vitamin D Receptor

    PubMed Central

    Garay, Edward; Donnelly, Robert; Wang, Xuening; Studzinski, George P.

    2010-01-01

    The anti-neoplastic effects of 1,25-dihydroxyvitamin D3 (1,25D) are well documented in numerous tumor cell systems and animal models of cancer. However, despite this pre-clinical success, the clinical use of 1,25D is currently impeded by the dose-limiting hypercalcemia, and the risk of development of resistance to 1,25D. In this study, we investigated the mechanism of resistance to 1,25D of HL60-40AF cells, a model of drug-resistant acute myeloid leukemia, derived from HL60 cells by cultivation in the presence of 1,25D. The data indicate that transcriptional activity of vitamin D receptor (VDR) in 40AF cells increases only briefly when the cells are treated with 1,25D, despite greater basal cellular levels of VDR protein in the resistant than in the 1,25D-sensitive cells. Analysis of the 40AF VDR mRNA sequence indicated alterations in the 5? untranslated region (UTR), but coding domain variations were not observed. When resistance to 1,25D-induced differentiation of 40AF cells was reversed by a combination of 1,25D with potentiators of differentiation (plant derived antioxidants and a p38MAPK inhibitor), an increase in the level of nuclear VDR, as well as an increase in CYP24 mRNA expression was observed. These data suggest that decreased ability of 1,25D to induce VDR nuclear localization and the consequent VDR target gene transcription may be an important reason for the resistance of 40AF cells to 1,25D. Further, our data show that VDR localization and phosphorylation can be increased by combining 1,25D with potentiators of differentiation. Analysis of the mechanisms that underlie the reduction and potentiation of 1,25D-mediated changes in VDR activity may lead to the identification of new cellular targets that enhance 1,25D-induced monocytic differentiation. PMID:17520689

  6. [Molecular targeted therapy in lymphoid leukemias].

    PubMed

    Kojima, Kensuke; Ando, Toshihiko; Kimura, Shinya

    2014-06-01

    Recent advances in the treatment of lymphoid leukemias have incorporated molecular targeted drugs (CD20-targeting rituximab and BCR-ABL tyrosine kinase inhibitors) into the traditional chemotherapeutic agents. This article reviews novel molecular targeted therapies for patients with lymphoid leukemias including acute lymphoblastic leukemia, chronic lymphocytic leukemia, hairly cell leukemia and HTLV-I-related adult T-cell leukemia. Investigational agents that will be discussed in this review include inotuzumab, blinatumomab, alemtuzumab, ofatumumab, ibrutinib, idelalisib, bafetinib, lenalidomide, ABT-199 and mogamulizumab. Novel approaches warrant continued research to improve outcomes for patients with lymphoid leukemias. PMID:25016810

  7. Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus

    SciTech Connect

    Iki, Shigeo [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Hokkaido Institute of Public Health, Kita-ku, Sapporo 060-0819 (Japan); Yokota, Shin-ichi [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Okabayashi, Tamaki [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Yokosawa, Noriko [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan); Nagata, Kyosuke [Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575 (Japan); Fujii, Nobuhiro [Department of Microbiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556 (Japan)]. E-mail: fujii@sapmed.ac.jp

    2005-12-05

    The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection.

  8. Pathogenesis and treatment of human T-cell leukemia virus infection

    Microsoft Academic Search

    Lee Ratner

    2005-01-01

    The pathogenesis of human T-cell leukemia virus (HTLV)-induced adult T-cell leukemia-lymphoma (ATLL) was explored using an\\u000a infectious molecular viral clone and a transgenic mouse model. Activation of nuclear factor-?B by the HTLV transcriptional\\u000a transactivator protein Tax was found to be important for lymphocyte immortalization and tumorigenesis. Interferon-? regulates\\u000a tumor development owing primarily to angiostatic effects. Translational clinical studies of chemotherapy,

  9. Body-wave magnitudes of underground nuclear explosions at major test sites derived by the maximum-likelihood method

    NASA Astrophysics Data System (ADS)

    Peacock, Sheila; Douglas, Alan; Bowers, David; Selby, Neil

    2013-04-01

    Body-wave magnitudes (mb) of ~600 underground nuclear tests have been derived from station amplitudes collected by the International Seismological Centre (ISC), by a joint inversion for mb and station-specific magnitude corrections (Lilwall 1986). The maximum-likelihood method was used, to reduce the upward bias of network mean magnitudes caused by data censoring for low-magnitude disturbances where stations do not report arrivals that are hidden by the ambient noise at the time. Threshold noise levels at each station were derived from the ISC amplitudes using the method of Kelly and Lacoss (1969). The joint inversion is valid only for sites where enough explosions occurred, and stations with enough arrivals (a minimum of three for both), for a statistical treatment to be valid. It is used on the sites: Kazakhstan and Novaya Zemlya, former Soviet Union; Singer, China; Mururoa and Fangataufa, French Polynesia; and Nevada, USA. At sites where four or more arrivals could be used to derive magnitudes and station terms for twenty-five or more explosions (Nevada, Kazakhstan and Mururoa), the resulting magnitudes and station terms were fixed and a second inversion carried out to derive magnitudes for additional explosions with as few as three arrivals. A further ~90 magnitudes were derived thus, mostly of Nevada explosions.

  10. What's New in Childhood Leukemia Research and Treatment?

    MedlinePLUS

    ... resources for childhood leukemia What’s new in childhood leukemia research and treatment? Researchers are now studying the ... chronic myeloid leukemia (CML)? Immunotherapy to treat childhood leukemia are treatments that boost a child’s own immune ...

  11. Chronic Myelomonocytic Leukemia (CMML) and Juvenile Myelomonocytic Leukemia (JMML)

    MedlinePLUS

    ... attack the disease (graft-versus-leukemia effect). The theory being tested with a reduced-intensity transplant is ... syndrome. These typically include heart malformation, short stature, learning disabilities, indentation of the chest, impaired blood clotting ...

  12. Functional Domain Structure of Human T-Cell Leukemia Virus Type 2 Rex

    Microsoft Academic Search

    Murli Narayan; Ihab Younis; Donna M. D'Agostino; Patrick L. Green

    2003-01-01

    The Rex protein of human T-cell leukemia virus (HTLV) acts posttranscriptionally to induce the cytoplasmic expression of the unspliced and incompletely spliced viral RNAs encoding the viral structural and enzymatic proteins and is therefore essential for efficient viral replication. Rex function requires nuclear import, RNA binding, multimerization, and nuclear export. In addition, it has been demonstrated that the phosphorylation status

  13. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-02-25

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-23

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  15. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  16. Targeted alpha particle immunotherapy for myeloid leukemia.

    PubMed

    Jurcic, Joseph G; Larson, Steven M; Sgouros, George; McDevitt, Michael R; Finn, Ronald D; Divgi, Chaitanya R; Ballangrud, Ase M; Hamacher, Klaus A; Ma, Dangshe; Humm, John L; Brechbiel, Martin W; Molinet, Roger; Scheinberg, David A

    2002-08-15

    Unlike beta particle-emitting isotopes, alpha emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the beta-emitters (131)I and (90)Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of beta-emitting constructs, the alpha-emitting isotope (213)Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg (213)Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the (213)Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with beta-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of (213)Bi-HuM195, and it is the first proof-of-concept for systemic targeted alpha particle immunotherapy in humans. PMID:12149203

  17. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2015-03-31

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. State-dependent calculation of three-body cluster energy for nuclear matter and the validity of the lowest order constrained variational formalism

    SciTech Connect

    Modarres, M.; Rajabi, A.; Moshfegh, H. R. [Physics Department, University of Tehran, North-Kargar Ave., 1439955961 Tehran (Iran, Islamic Republic of)

    2007-12-15

    It is shown that the method of lowest order constrained variational (LOCV) which is based on the cluster expansion theory is a reliable many-body technique to calculate the nuclear matter equation of state. In this respect, the state dependent correlation functions and the effective interactions which have been produced by the LOCV calculation with the Reid and {delta}-Reid soft core interactions are used to estimate the size of higher order cluster terms such as the effect of three-body cluster energy on the nuclear matter ground state energy. Finally it is shown that the LOCV normalization constraint plays a major role in the convergence of the cluster expansion and the result of LOCV calculation can be as good as more sophisticated approaches which go beyond lowest order.

  19. Genetic predispositions to childhood leukemia

    PubMed Central

    Stieglitz, Elliot

    2013-01-01

    While the majority of leukemia cases occur in the absence of any known predisposing factor, there are germline mutations that significantly increase the risk of developing hematopoietic malignancies in childhood. In this review article, we describe a number of these mutations and their clinical features. These predispositions can be broadly classified as those leading to bone marrow failure, those involving tumor suppressor genes, DNA repair defects, immunodeficiencies or other congenital syndromes associated with transient myeloid disorders. While leukemia can develop as a secondary event in the aforementioned syndromes, there are also several syndromes that specifically lead to the development of leukemia as their primary phenotype. Many of the genes discussed in this review can also be somatically mutated in other cancers, highlighting the importance of understanding shared alterations and mechanisms underpinning syndromic and sporadic leukemia. PMID:23926459

  20. Emergencies in Acute Lymphoblastic Leukemia

    Microsoft Academic Search

    Olga Frankfurt; Martin S. Tallman

    The clinical presentation of acute lymphoblastic leukemia (ALL) may range from nonspecific symptoms such as progressive malaise,\\u000a fever, and fatigue to severe life-threatening manifestations, requiring immediate medical intervention.

  1. How Is Childhood Leukemia Classified?

    MedlinePLUS

    ... in immature forms of cells that make platelets. World Health Organization (WHO) classification of AML The FAB ... phases, but a common system (proposed by the World Health Organization) is described below. If the leukemia ...

  2. Management of chronic lymphocytic leukemia

    PubMed Central

    Ghia, Paolo; Hallek, Michael

    2014-01-01

    In the last decade, the management of chronic lymphocytic leukemia has undergone profound changes that have been driven by an improved understanding of the biology of the disease and the approval of several new drugs. Moreover, many novel drugs are currently under evaluation for rapid approval or have been approved by regulatory agencies, further broadening the available therapeutic armamentarium for patients with chronic lymphocytic leukemia. The use of novel biological and genetic parameters combined with a careful clinical evaluation allows us to dissect some of the heterogeneity of the disease and to distinguish patients with a very mild onset and course, who often will not need any treatment, from those with an intermediate prognosis and a third group with a very aggressive course (high-risk leukemia). On this background, it becomes increasingly challenging to select the right treatment strategy. In this paper, we describe our own approach to the management of different patients with chronic lymphocytic leukemia. PMID:24881042

  3. Progress in acute myeloid leukemia.

    PubMed

    Kadia, Tapan M; Ravandi, Farhad; O'Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M

    2015-03-01

    Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

  4. ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes to the PML nuclear bodies and interacts with SUMO-1 and PML

    SciTech Connect

    Kunapuli, Padmaja [Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Kasyapa, Chitta S. [Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Chin, Suet-Feung [Cancer Genomics Program, Hutchison/MRC Research Centre, Cambridge CB2 2XZ (United Kingdom); Caldas, Carlos [Cancer Genomics Program, Hutchison/MRC Research Centre, Cambridge CB2 2XZ (United Kingdom); Cowell, John K. [Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States)]. E-mail: John.Cowell@RoswellPark.org

    2006-11-15

    The ZNF198/FGFR1 fusion gene in atypical myeloproliferative disease produces a constitutively active cytoplasmic tyrosine kinase, unlike ZNF198 which is normally a nuclear protein. We have now shown that the ZNF198/FGFR1 fusion kinase interacts with the endogenous ZNF198 protein suggesting that the function of ZNF198 may be compromised in cells expressing it. Little is currently known about the endogenous function of ZNF198 and to investigate this further we performed a yeast two-hybrid analysis and identified SUMO-1 as a binding partner of ZNF198. These observations were confirmed using co-immunoprecipitation which demonstrated that ZNF198 is covalently modified by SUMO-1. Since many of the SUMO-1-modified proteins are targeted to the PML nuclear bodies we used confocal microscopy to show that SUMO-1, PML and ZNF198 colocalize to punctate structures, shown by immunocytochemistry to be PML bodies. Using co-immunoprecipitation we now show that PML and sumoylated ZNF198 can be found in a protein complex in the cell. Mutation of the SUMO-1 binding site in wild-type ZNF198 resulted in loss of distinct PML bodies, reduced PML levels and a more dispersed nuclear localization of the PML protein. In cells expressing ZNF198/FGFR1, which also lack the SUMO-1 binding site, SUMO-1 is preferentially localized in the cytoplasm, which is associated with loss of distinct PML bodies. Recently, arsenic trioxide (ATO) was proposed as an alternative therapy for APL that was resistant to traditional therapy. Treatment of cells expressing ZNF198/FGFR1 with ATO demonstrated reduced autophosphorylation of the ZNF198/FGFR1 protein and induced apoptosis, which is not seen in cells expressing wild-type ZNF198. Overall our results suggest that the sumoylation of ZNF198 is important for PML body formation and that the abrogation of sumoylation of ZNF198 in ZNF198/FGFR1 expressing cells may be an important mechanism in cellular transformation.

  5. Molecular diagnosis of lymphoblastic leukemia.

    PubMed

    Goud, Kalal Iravathy; Dayakar, Seetha; Prasad, S V S S; Rao, Koteshwar N; Shaik, Amina; Vanjakshi, S

    2013-01-01

    The mixed lineage leukemia (MLL) gene at chromosome band 11q23 is commonly involved in reciprocal translocations that is detected in acute leukemia. The MLL gene, commonly known as mixed lineage leukemia or myeloid lymphoid leukemia, has been independently identified and cloned from the 11q23 breakpoint of acute leukemia. We describe a patient with acute lymphoblastic leukemia whose cells had shown reciprocal translocation between short arm (p21) of chromosome 2 and long arm (q23) of chromosome number 11 [t(2;11) (p21;q23)] by cytogenetic analysis. Fluorescence in situ hybridization analysis (FISH) was also performed for reconfirmation with a probe for MLL which showed split signals, hybridizing to both the derivative 2 and 11 chromosomes. Our study confirmed FISH as the most suitable assay for detecting MLL rearrangements because of its sensitivity and speed. It recommended that FISH should be used as complementary to conventional cytogenetic analysis. In conclusion, evaluation of the t(2;11)(p21;q23) was done by molecular clarification and flow cytometry. PMID:24125990

  6. Reciprocal leukemia-stroma VCAM-1/VLA-4-dependent activation of NF-?B mediates chemoresistance.

    PubMed

    Jacamo, Rodrigo; Chen, Ye; Wang, Zhiqiang; Ma, Wencai; Zhang, Min; Spaeth, Erika L; Wang, Ying; Battula, Venkata L; Mak, Po Yee; Schallmoser, Katharina; Ruvolo, Peter; Schober, Wendy D; Shpall, Elizabeth J; Nguyen, Martin H; Strunk, Dirk; Bueso-Ramos, Carlos E; Konoplev, Sergej; Davis, R Eric; Konopleva, Marina; Andreeff, Michael

    2014-04-24

    Leukemia cells are protected from chemotherapy-induced apoptosis by their interactions with bone marrow mesenchymal stromal cells (BM-MSCs). Yet the underlying mechanisms associated with this protective effect remain unclear. Genome-wide gene expression profiling of BM-MSCs revealed that coculture with leukemia cells upregulated the transcription of genes associated with nuclear factor (NF)-?B signaling. Moreover, primary BM-MSCs from leukemia patients expressed NF-?B target genes at higher levels than their normal BM-MSC counterparts. The blockade of NF-?B activation via chemical agents or the overexpression of the mutant form of inhibitor ?B-? (I?B?) in BM-MSCs markedly reduced the stromal-mediated drug resistance in leukemia cells in vitro and in vivo. In particular, our unique in vivo model of human leukemia BM microenvironment illustrated a direct link between NF-?B activation and stromal-associated chemoprotection. Mechanistic in vitro studies revealed that the interaction between vascular cell adhesion molecule 1 (VCAM-1) and very late antigen-4 (VLA-4) played an integral role in the activation of NF-?B in the stromal and tumor cell compartments. Together, these results suggest that reciprocal NF-?B activation in BM-MSCs and leukemia cells is essential for promoting chemoresistance in the transformed cells, and targeting NF-?B or VLA-4/VCAM-1 signaling could be a clinically relevant mechanism to overcome stroma-mediated chemoresistance in BM-resident leukemia cells. PMID:24599548

  7. Clinical and hematological profile of acute megakaryoblastic leukemia: a 2 year study.

    PubMed

    Jayasudha, A V; Nair, Rekha A; Jacob, Priya Mary; Renu, S; Anila, K R; Sindhu Nair, P; Priya Kumari, T; Kusuma Kumary, P

    2015-06-01

    Acute megakaryoblastic leukemia is a rare subtype of acute myeloid leukemia with a characteristic morphologic and immunophenotypic profile. It has to be distinguished from other subtypes of acute myeloid leukemia as well as acute myeloid leukemia with t (1; 22) (p13;q13) and acute megakaryoblastic leukemia in Down Syndrome because of its poor prognosis. We studied ten cases diagnosed over a period of 2 years (from July 2011 to June 2013). All the ten cases were in the pediatric age group ranging from 4 months to 2 years. On morphology, pointers to the diagnosis were clustering of blasts, presence of cytoplasmic blebs and platelet budding. An additional interesting morphological feature observed in our study was nuclear blebs which were seen in nine cases. Diagnosis was confirmed in all cases by positive immunostaining for CD61. Two of the cases had an extremely rare clinical presentation as granulocytic sarcoma. Although rare, acute megakaryoblastic leukemia should be kept in mind especially in leukemia in infants. PMID:25825554

  8. [Acute myeloid leukemia].

    PubMed

    Döhner, K; Paschka, P; Döhner, H

    2015-04-01

    In recent years, the development of novel molecular techniques has been instrumental in deciphering the genetic heterogeneity of acute myeloid leukemia (AML) as well as in gaining important insights into the pathomechanisms of AML. Genetic diagnostics has become an essential component in the initial work-up for disease classification, prognostication, and genotype-specific therapies. A major prerequisite for such individualized treatment strategies is a rapid pretherapeutic genetic analysis, which includes screening for the recurrent AML-associated gene fusions as well as mutations in the genes NPM1, FLT3, and CEBPA. Some of these molecular markers can be used for monitoring minimal residual disease and therefore provide clinically relevant information. There is an increasing number of promising molecularly targeted therapies in clinical development for distinct genetic AML subgroups. Solid data exist for the combination of all-trans retinoic acid and arsentrioxid in the treatment of acute promyelocytic leukemia; the addition of the immunoconjugate gemtuzumab ozogamicin (GO) to induction therapy has been shown to improve outcome in cytogenetic low- and intermediate-risk AML. Furthermore, there are encouraging data on the combination of intensive chemotherapy with tyrosine kinase inhibitors in patients with AML harboring FLT3 mutations or with core-binding factor AML. Other novel therapeutic approaches address mutations or alterations in epigenetic regulators, such as IDH or DOT1L inhibitors. The comprehensive characterization of the underlying genetic mechanisms is essential for the development of novel target-specific compounds with the aim of improving outcome in AML patients. PMID:25787321

  9. [Juvenile myelomonocytic leukemias].

    PubMed

    Lachenaud, Julie; Strullu, Marion; Baruchel, André; Cavé, Hélène

    2014-03-01

    Juvenile myelomonocytic leukemias (JMML) are rare but severe myelodysplastic and myeloproliferative neoplasms of infancy. They represent about 10 new cases per year in France and preferentially affect males. JMML are all stem cell diseases the common denominator of which is RAS pathway dysregulation, due to mutations in RAS (NRAS, KRAS) or RAS regulatory components (PTPN11, NF1 or CBL). This leads to an hypersensivity of myeloid progenitors to GM-CSF (granulo-macrophagic colony stimulating factor) which induces in turn excessive monocytic and macrophagic proliferation in blood and bone marrow. All organs can be infiltrated by this monocytic proliferation leading to multisystemic failure. Blast crisis with transformation into acute myeloid leukemia occurs in one third of patients. A salient feature of JMML is their frequent association with predisposition syndromes such as Noonan syndrome, neurofibromatosis and CBL syndrome, which are developmental diseases associated with a constitutional RAS pathway deregulation, now grouped under the name RASopathies. Clinical heterogeneity makes JMML diagnosis difficult. Splenomagaly is the most constant sign. Palor, adenopathy, respiratory or cutaneous symptoms can also be present. Blood smear shows monocytosis (>1×10(9)/L) presence of myeloid progenitors and abnormal basophils. The demonstration of an endogeneous in vitro growth of myeloid progenitors although not very specific can help JMML diagnosis. Nowadays, genetic typing has to be included in the workup of JMML diagnosis and allows to evidence a mutation in more than 90% of cases. JMML have a poor prognosis. The only curative treatment is bone marrow transplantation but approximately 35% of patients relapse. JMML clinical course is highly heterogeneous and unpredictable. Some rare patients have an indolent evolution or even spontaneous remission. Age over two years, thrombopenia below 33×10(9)/L and high foetal hemoglobin (HbF) level for age are poor prognosis criteria but hardly predict individual outcome. Several research directions are currently being explored to improve prognosis prediction and provide more effective targeted treatments. PMID:24691193

  10. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Gastric myeloid sarcoma without acute myeloblastic leukemia

    PubMed Central

    Huang, Xiao-Li; Tao, Jin; Li, Jian-Zhong; Chen, Xiao-Liang; Chen, Jian-Ning; Shao, Chun-Kui; Wu, Bin

    2015-01-01

    Myeloid sarcomas (MS) involve extramedullary blast proliferation from one or more myeloid lineages that replace the original tissue architecture, and these neoplasias are called granulocytic sarcomas, chloromas or extramedullary myeloid tumors. Such tumors develop in lymphoid organs, bones (e.g., skulls and orbits), skin, soft tissue, various mucosae, organs, and the central nervous system. Gastrointestinal (GI) involvement is rare, while the occurrence of myeloid sarcomas in patients without leukemia is even rare. Here, we report a case of a 38-year-old man who presented with epigastric pain and progressive jaundice. An upper GI endoscopy had shown extensive multifocal hyperemic fold thickening and the spread of nodular lesions in the body of the stomach. Biopsies from the gastric lesions indicated myeloid sarcoma of the stomach. However, concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia. For diagnosis, the immunohistochemical markers must be checked when evaluating a suspected myeloid sarcoma case. Accurate MS diagnosis determines the appropriate therapy and prognosis. PMID:25717265

  12. LLNL's Regional Model Calibration and Body-Wave Discrimination Research in the Former Soviet Union using Peaceful Nuclear Explosions (PNEs)

    SciTech Connect

    Bhattacharyya, J.; Rodgers, A.; Swenson, J.; Schultz, C.; Walter, W.; Mooney, W.; Clitheroe, G.

    2000-07-14

    Long-range seismic profiles from Peaceful Nuclear Explosions (PNE) in the Former Soviet Union (FSU) provide a unique data set to investigate several important issues in regional Comprehensive Nuclear-Test-Ban Treaty (CTBT) monitoring. The recording station spacing ({approx}15 km) allows for extremely dense sampling of the propagation from the source to {approx} 3300 km. This allows us to analyze the waveforms at local, near- and far-regional and teleseismic distances. These data are used to: (1) study the evolution of regional phases and phase amplitude ratios along the profile; (2) infer one-dimensional velocity structure along the profile; and (3) evaluate the spatial correlation of regional and teleseismic travel times and regional phase amplitude ratios. We analyzed waveform data from four PNE's (m{sub b} = 5.1-5.6) recorded along profile KRATON, which is an east-west trending profile located in northern Sibertil. Short-period regional discriminants, such as P/S amplitude ratios, will be essential for seismic monitoring of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) at small magnitudes (m{sub b} < 4.0). However, P/S amplitude ratios in the short-period band, 0.5-5.0 Hz, show some scatter. This scatter is primarily due to propagation and site effects, which arise from variability in the elastic and anelastic structure of the crustal waveguide. Preliminary results show that Pg and Lg propagate efficiently in north Siberia at regional distances. The amplitude ratios show some variability between adjacent stations that are modeled by simple distance trends. The effect of topography, sediment and crustal thickness, and upper mantle discontinuities on these ratios, after removal of the distance trends, will be investigated. The travel times of the body wave phases recorded on KEATON have been used to compute the one-dimensional structure of the crust and upper mantle in this region. The path-averaged one-dimensional velocity model was computed by minimizing the first arriving P-phase travel-time residuals for all distances ({Delta} = 300-2300 km). A grid search approach was used in the minimization. The most significant features of this model are the negative lid-gradient and a low-velocity zone in the upper mantle between the depths of 100-200 km; precise location of the LVZ is poorly constrained by the travel time data. We will extend our investigation to additional PNE lines to further investigate the amplitude and travel-time variations in eastern and central Eurasia. Finally, the dense station spacing of the PNE profiles allows us to model the spatial correlation of travel times and amplitude ratios through variogram modeling. The statistical analysis suggests that the correlation lengths of the travel-time and amplitude measurements are 12{sup o} and 10{sup o}, respectively.

  13. Nuclear shape, growth and integrity in the closed mitosis of fission yeast depend on the Ran-GTPase system, the spindle pole body and the endoplasmic reticulum

    PubMed Central

    Gonzalez, Yanira; Meerbrey, Kristen; Chong, Jennifer; Torii, Yoshihiro; Padte, Neal N.; Sazer, Shelley

    2009-01-01

    Summary The double lipid bilayer of the nuclear envelope (NE) remains intact during closed mitosis. In the fission yeast Schizosaccharomyces pombe, the intranuclear mitotic spindle has envelope-embedded spindle pole bodies (SPB) at its ends. As the spindle elongates and the nucleus divides symmetrically, nuclear volume remains constant but nuclear area rapidly increases by 26%. When Ran-GTPase function is compromised in S. pombe, nuclear division is strikingly asymmetrical and the newly synthesized SPB is preferentially associated with the smaller nucleus, indicative of a Ran-dependent SPB defect that interferes with symmetrical nuclear division. A second defect, which specifically influences the NE, results in breakage of the NE upon spindle elongation. This defect, but not asymmetric nuclear division, is partially rescued by slowing spindle elongation, stimulating endoplasmic reticulum (ER) proliferation or changing conformation of the ER membrane. We propose that redistribution of lipid within the ER-NE network is crucial for mitosis-specific NE changes in both open and closed mitosis. PMID:19571115

  14. Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2015-05-01

    B-cell Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  15. MLL leukemia and future treatment strategies.

    PubMed

    Marschalek, Rolf

    2015-04-01

    Chromosomal rearrangements of the MLL gene are associated with high-risk infant, pediatric, adult, and therapy-induced acute leukemias. So far, about 80 different direct MLL fusions and about 120 reciprocal MLL fusions have been characterized at the molecular level. The common theme in these leukemia-associated genetic rearrangements is the genetic disruption of the MLL gene. This leads to MLL-X fusion proteins that still bind to nuclear factors (e.g., MEN1, LEDGF), which in turn allow them to target promoters and cause ectopic gene transcription. In addition, the most frequent MLL fusions (MLL-AF4, MLL-AF9, MLL-AF10, and MLL-ENL) are all recruiting the wild-type AF4 multiprotein complex that contains the target proteins P-TEFb, BRD4, and DOT1L. Vice versa, reciprocal X-MLL fusions exhibit a PHD domain (H3K4me3 reader domain), sequester the histone acetyltransferases CREBBP and MOF1 and bear a histone methyltransferase domain at their very C-terminus (SET domain). Except for AF4-MLL, the functional consequences deriving from reciprocal fusion proteins are not very well understood. However, based on our knowledge about the above-mentioned MLL fusions, it is reasonable to inhibit their oncogenic activity in a targeted fashion. Recent efforts in developing such inhibitors and their mode of action will be critically discussed. PMID:25740345

  16. Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study.

    PubMed

    Stevens, W; Thomas, D C; Lyon, J L; Till, J E; Kerber, R A; Simon, S L; Lloyd, R D; Elghany, N A; Preston-Martin, S

    1990-08-01

    Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation. PMID:2366297

  17. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePLUS

    ... Parents > Diseases & Conditions > Cancer & Tumors > Acute Lymphoblastic Leukemia (ALL) Print A A A Text Size What's in ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

  18. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePLUS

    ... abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets. Adult acute myeloid leukemia ( ... is made mostly of fat. Leukemia may affect red blood cells, white blood cells, and platelets. Normally, ...

  19. Childhood leukemia in Woburn, Massachusetts

    SciTech Connect

    Cutler, J.J.; Parker, G.S.; Rosen, S.; Prenney, B.; Healey, R.; Caldwell, G.G.

    1986-03-01

    Possible associations between environmental hazards and the occurrence of childhood leukemia were investigated in Woburn, MA, for the period 1969-79. Residents of Woburn were concerned over what they perceived to be a large number of childhood leukemia cases; at the same time there was extensive publicity about uncontrolled hazardous waste sites in Woburn, which resulted in its being placed on the Superfund list. Many believed that the elevated rate of childhood leukemia was related to these sites or to two city water wells that had been closed in 1979 when they were found to be contaminated by organic chemicals. An occurrence was defined as childhood leukemia when it was diagnosed in a Woburn resident less than 20 years old between 1969 and 1979 and confirmed by review of hospital and pathology records. This investigation confirmed an increase in incidence which was distributed uniformly over the 11-year period. Six of the persons with leukemia were located close to each other in one census tract, 7.5 times the expected number. Parents of the children and of two matched control groups were interviewed about medical history, mother's pregnancy history, school history, and environmental exposures. There were no significant differences between the leukemia victims and persons in the control groups. No leukemia sufferer had contact with a hazardous waste site. While the contaminants of Wells G and H, which had been closed, are not known leukemogens, it is not possible to rule out exposure to this water as a factor, particularly in the eastern Woburn residents.

  20. The Childhood Leukemia International Consortium

    PubMed Central

    Metayer, Catherine; Milne, Elizabeth; Clavel, Jacqueline; Infante-Rivard, Claire; Petridou, Eleni; Taylor, Malcolm; Schüz, Joachim; Spector, Logan G.; Dockerty, John D.; Magnani, Corrado; Pombo-de-Oliveira, Maria S.; Sinnett, Daniel; Murphy, Michael; Roman, Eve; Monge, Patricia; Ezzat, Sameera; Mueller, Beth A.; Scheurer, Michael E.; Armstrong, Bruce K.; Birch, Jill; Kaatsch, Peter; Koifman, Sergio; Lightfoot, Tracy; Bhatti, Parveen; Bondy, Melissa L.; Rudant, Jérémie; O’Neill, Kate; Miligi, Lucia; Dessypris, Nick; Kang, Alice Y.; Buffler, Patricia A.

    2013-01-01

    Background Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic groups. PMID:23403126

  1. Rapidly progressive myelomonocytic leukemia (juvenile CML).

    PubMed

    Bacon, D R; Mosijczuk, A D; Humberd, Q A

    1986-01-01

    A rare type of rapidly fatal childhood leukemia, generally called juvenile chronic myelogenous leukemia, is characterized by absence of the Philadelphia chromosome and a predominantly monocytic proliferation, among other features. Unlike Philadelphia chromosome positive chronic myelogenous leukemia, this disease is neither chronic nor principally a disorder of granulocytic cell lines. A case is presented, with several clinical and laboratory parameters useful in establishing the correct diagnosis, and a change in terminology to "rapidly progressive juvenile myelomonocytic leukemia" is proposed. PMID:3473455

  2. Graft-versus-leukemia in rat MHC-mismatched bone marrow transplantation is merely an allogeneic effect.

    PubMed

    Kloosterman, T C; Martens, A C; van Bekkum, D W; Hagenbeek, A

    1995-04-01

    One of the major problems in the treatment of leukemia with bone marrow transplantation (BMT) remains leukemia relapse. It has been clearly shown that graft-versus-host disease (GVHD) is accompanied by a graft-versus-leukemia reaction (GVLR) which reduces the incidence of leukemia relapse. To date, discussion is still going on as to whether GVHD and GVLR are either two different reactions or are exerting their effects through the same mechanism(s). In two rat leukemia models, namely the Brown Norway acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia L4415, total body irradiation (TBI) was given to induce a state of so-called minimal residual disease (MRD). Subsequently, it was attempted to evoke a GVLR distinct from GVHD by using semi-allogeneic hybrid-to-parent or parent-to-hybrid BMT, with or without the addition of graded numbers of lymphocytes. In both leukemia models applying hybrid-to-parent BMT, the addition of high numbers of semi-allogeneic lymphocytes to the semi-allogeneic graft had no antileukemic effect. In parent-to-hybrid BMT, the grafts sharing their alloantigens with the leukemia cells did not induce an anti-leukemic effect, irrespective of the number of lymphocytes present in the graft or the induction of evident GVHD. When the parental graft was histoincompatible with the leukemia cells, transplantation of bone marrow alone induced a significant increase in life span correlating with 2.8 log leukemia cell kill (LCK).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7655385

  3. [Chronic lymphatic leukemia].

    PubMed

    Bergmann, Manuela; Wendtner, Clemens-Martin

    2015-04-01

    Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western world. Median age at diagnosis is around 70 years. To confirm the diagnosis more than 5000 B-lymphocytes/µl need to be present. The expression of the typical surface markers CD5, CD19, CD20 and CD23 has to be confirmed by flow cytometry. A bone marrow biopsy is not mandatory for the diagnosis. Before start of treatment the assessment of 17?p deletion and/or TP53-mutational status is recommended. Treatment indications include stage Binet C or signs of an active disease as rapidly progressive lymphadenopathy or organomegaly together with physical limitation, B symptoms that cannot be tolerated, rapidly deteriorating blood values, or rapidly increasing leukocyte counts (Lymphocyte doubling time less than 6 months). The patient's physical condition has major impact on the treatment decision. Currently immunochemotherapy with fludarabine, cyclophosphamide and the CD20-antibody rituximab (FCR) is the standard of care in previously untreated and physically fit patients. An alternative regimen is the combination of bendamustine and rituximab (BR) or ofatumumab. Physically compromised patients can be treated with the oral drug chlorambucil in combination with an anti-CD20 antibody. Due to high morbidity and mortality, allogeneic stem cell transplantation is limited to a small group of patients and should be discussed in a high-risk situation, such as 17?p deletion and/or TP53-mutation, lack of response to standard therapy or early relapse. Recently several new chemo-free treatment options have been introduced within clinical trials. Among them are monoclonal antibodies, most of them targeting the CD20 molecule: besides the licensed drugs rituximab and ofatumumab, obinutuzumab, in combination with chemotherapy, has recently shown high clinical efficacy in front-line treatment of elderly patients with CLL. Novel agents have been designed to block aberrant signaling from the B-cell receptor. Ibrutinib acts by inhibiting the Bruton's tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform. Another class of drugs with potential impact for chemo-free treatment strategies in CLL is the BH3-mimetic inhibitor of the Bcl-2 family of pro-survival proteins, ABT-199. Given all these novel agents and targets, chemo-free or at least chemo-reduced concepts may become reality in the near future for our patients suffering from CLL. PMID:25826029

  4. LEADING ARTICLE Proteomic analysis of childhood leukemia

    E-print Network

    California at Berkeley, University of

    LEADING ARTICLE Proteomic analysis of childhood leukemia CM Hegedus1 , L Gunn1 , CF Skibola1 , L of Hematology-Oncology, Stanford, CA, USA Childhood acute lymphoblastic and myeloid leukemias are stratified expression profiles can discriminate between leukemia sub- types. Thus, proteome analysis similarly holds

  5. Review article Pathobiology of bovine leukemia virus

    E-print Network

    Boyer, Edmond

    Review article Pathobiology of bovine leukemia virus I Schwartz D Lévy URA-INRA d-Alfort cedex, France (Received 16 March 1994; accepted 25 July 1994) Summary ― Bovine leukemia virus (BLV) is a retrovirus similar to the human T-cell leukemia virus (HTLV). Most BLV infected animals (70

  6. Deterministic Model for Acute Myelogenous Leukemia Classification

    E-print Network

    Chronopoulos, Anthony T.

    Deterministic Model for Acute Myelogenous Leukemia Classification Monica Madhukar-- Leukemia is a type of cancer that affects the blood and the bone marrow. Manual data analysis is time that the proposed system robustly segments and classifies Acute Myelogenous Leukemia based on complete microscopic

  7. Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-23

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  8. Department of Mechanical and Nuclear Engineering Spring 2011 Shell 1 -Battery Electric Vehicle Chassis and Body Design

    E-print Network

    Demirel, Melik C.

    to the previous hydrogen fuel cell. Since the team was making the vehicle smaller, a smaller more aerodynamic body Vehicle Chassis and Body Design Overview The team faced the challenging task of redesigning a previous Penn State Shell Eco-marathon vehicle to accommodate a battery operated powertrain as opposed

  9. Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

    PubMed Central

    Giovannoni, Federico; Damonte, Elsa B.; García, Cybele C.

    2015-01-01

    The intrinsic antiviral defense is based on cellular restriction factors that are constitutively expressed and, thus, active even before a pathogen enters the cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear foci that contain several cellular proteins involved in intrinsic antiviral responses against a number of viruses. Accumulating reports have shown the importance of PML as a DNA virus restriction factor and how these pathogens evade this antiviral activity. However, very little information is available regarding the antiviral role of PML against RNA viruses. Dengue virus (DENV) is an RNA emerging mosquito-borne human pathogen affecting millions of individuals each year by causing severe and potentially fatal syndromes. Since no licensed antiviral drug against DENV infection is currently available, it is of great importance to understand the factors mediating intrinsic immunity that may lead to the development of new pharmacological agents that can boost their potency and thereby lead to treatments for this viral disease. In the present study, we investigated the in vitro antiviral role of PML in DENV-2 A549 infected cells. PMID:25962098

  10. PLASMA CELL LEUKEMIA

    PubMed Central

    de Larrea, Carlos Fernandez; Kyle, Robert A.; Durie, Brian GM; Ludwig, Heinz; Usmani, Saad; Vesole, David H.; Hajek, Roman; Miguel, Jésus San; Sezer, Orhan; Sonneveld, Pieter; Kumar, Shaji K.; Mahindra, Anuj; Comenzo, Ray; Palumbo, Antonio; Mazumber, Amitabha; Anderson, Kenneth C.; Richardson, Paul G.; Badros, Ashraf Z.; Caers, Jo; Cavo, Michele; LeLeu, Xavier; Dimopoulos, Meletios A.; Chim, CS; Schots, Rik; Noeul, Amara; Fantl, Dorotea; Mellqvist, Ulf-Henrik; Landgren, Ola; Chanan-Khan, Asher; Moreau, Philippe; Fonseca, Rafael; Merlini, Giampaolo; Lahuerta, JJ; Bladé, Joan; Orlowski, Robert Z.; Shah, Jatin J.

    2014-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathologic entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (? 20%) and absolute number (? 2 × 10 9/L) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be reexamined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. PMID:23288300

  11. [Chronic myelogenous leukemia].

    PubMed

    Hochhaus, A; La Rosée, P; Eigendorff, E; Ernst, T

    2015-04-01

    The advent of tyrosine kinase inhibitors (TKI) has improved the prognosis and outcome of patients with chronic myelogenous leukemia (CML) considerably. Compared with imatinib, the first-line use of second-generation inhibitors nilotinib and dasatinib has led to faster and deeper molecular remissions accompanied by a differential adverse effect profile. An essential part of the management of CML patients is the guideline-based application of cytogenetics and standardized polymerase chain reaction techniques to regularly assess the remission status. Long-lasting treatment-free remission in a minority of patients led to hopes for the curability of CML in a significant minority of patients. The use of interferon alpha combined with or after TKI therapy is associated with the induction of an immune response toward the leukemic clone. This innovative treatment approach is currently under prospective investigation to improve long-term response. The coordinated cooperation of academic and regional hospitals, office-based hematologists, laboratories, and patient representatives allows for up-to-date patient care and the early use of new therapeutic options in patients at risk. PMID:25860113

  12. [Hypocellular acute leukemia].

    PubMed

    Tomonaga, M

    1995-05-01

    To establish diagnostic criteria for hypocellular acute leukemia (HL) 32 cases (mean age 67) with 40% or less bone marrow cellularity were analysed and compared with 40 cases of MDS, 27 cases of AML in the elderly (60 > or = ) and 39 cases of AML in the young (60 <). The mean bone marrow cellularity was 30% in HL, 85% in MDS, 87% in elderly AML and 95% in young AML, respectively. Thus hypocellularity was evident in HL. Blast % in bone marrow of HL patients was 17-70% in all nucleated cells including lymphocytes (ANC), 36-93% in non-lymphocytic cells (NLC) and 50% or more in all cases in non-erythroid/non-lymphocytic cells (NENLC). Thus maturation arrest of blast cells was evident in HL, which corresponds to that of overt AML. Out of 20 cases treated with low-dose ara-C 13 cases (65%) achieved complete remission, but most of them relapsed early by manifesting hypocellular bone marrow again. In conclusion HL is a distinct clinical subtype of AML in the elderly, which can be clearly defined by 40% or less cellularity and 30% or more blasts in bone marrow. PMID:7783351

  13. Management of Febrile Neutropenia in a Patient With Acute Leukemia

    PubMed Central

    Bryant, Ashley Leak; Walton, AnnMarie; Albrecht, Tara A.

    2013-01-01

    Hematologic cancers comprise an aggregate of several different cancers, such as leukemia, lymphoma, and multiple myeloma. There are more than 100,000 new cases of these hematologic cancers in the United States annually, and more than 50,000 children and adults die from these cancers.1,2 Hematologic cancers affect the body’s blood, bone marrow, and lymphatic system, leaving these patients more susceptible to infections.1 A newly diagnosed patient with acute leukemia receives aggressive chemotherapy treatment and is closely monitored in the hospital for at least 3 to 4 weeks. Treatment-related signs and symptoms including fever, pain, nausea and vomiting, and respiratory distress may bring the patient to the emergency department before his or her next scheduled clinic appointment.3,4 In this article a case study of a patient with acute lymphoblastic leukemia who enters the emergency department will be used to illustrate a common clinical scenario and provide clinical implications for emergency nurses who care for patients with hematologic cancers. PMID:24054730

  14. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-02

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-27

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Nuclear

    NSDL National Science Digital Library

    Iowa Public Television. Explore More Project

    2004-01-01

    What part does nuclear energy play in satisfying energy demands? This informational piece, part of a series about the future of energy, introduces students to the uranium atom as an energy source. Here students read about the history of nuclear energy, how energy is derived from uranium, and benefits of nuclear energy. Information is also provided about limitations, particularly disposal problems and radioactivity, and geographical considerations of nuclear power in the United States. Thought-provoking questions afford students chances to reflect on what they've read about the uses of nuclear power. Articles and information on new nuclear plant design and nuclear accidents are available from a sidebar. Five energy-related PBS NewsHour links are provided. A web link to the U.S. Nuclear Regulatory Commission is included. Copyright 2005 Eisenhower National Clearinghouse

  17. Infection and childhood leukemia: review of evidence

    PubMed Central

    Maia, Raquel da Rocha Paiva; Wünsch, Victor

    2013-01-01

    OBJECTIVE To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ? 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia. RESULTS Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori. CONCLUSIONS Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. PMID:24626555

  18. Pomalidomide After Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2015-05-06

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  19. Leukemia cutis presenting as a scrotal ulcer.

    PubMed

    Zax, R H; Kulp-Shorten, C L; Callen, J P

    1989-08-01

    A patient with acute nonlymphocytic leukemia developed a painful scrotal ulcer thought initially to be caused by infection. The lesion failed to heal with oral antibiotic therapy and local wound care. Histopathologic examination of a biopsy specimen revealed an infiltrate of leukemic cells. This cutaneous lesion heralded the relapse of acute myelogenous leukemia. A review of the literature indicates that acute nonlymphocytic leukemia rarely presents as an ulcer or on the genitalia, thus emphasizing the uniqueness of this case regarding morphology, and site of presentation. To our knowledge, this is the first case of leukemia cutis presenting as a scrotal ulcer. Therefore leukemia cutis should be added to the differential diagnosis of chronic genital ulcers. Also, because a variety of skin lesions may signify the relapse of leukemia, any skin lesion in a patient with leukemia should be examined by biopsy. PMID:2754075

  20. Plasma cell leukemia

    PubMed Central

    Albarracin, Flavio; Fonseca, Rafael

    2014-01-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/?L and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

  1. Donor Umbilical Cord Blood Transplant With or Without Ex-Vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-06-19

    Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Pancytopenia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia

  2. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2015-06-01

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  3. LLNL's Regional Model Calibration and Body-Wave Discrimination Research in the Former Soviet Union using Peaceful Nuclear Explosions (PNEs)

    Microsoft Academic Search

    J. Bhattacharyya; A. Rodgers; J. Swenson; C. Schultz; W. Walter; W. Mooney; G. Clitheroe

    2000-01-01

    Long-range seismic profiles from Peaceful Nuclear Explosions (PNE) in the Former Soviet Union (FSU) provide a unique data set to investigate several important issues in regional Comprehensive Nuclear-Test-Ban Treaty (CTBT) monitoring. The recording station spacing (â15 km) allows for extremely dense sampling of the propagation from the source to â 3300 km. This allows us to analyze the waveforms at

  4. Nuclear Scans

    MedlinePLUS

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  5. Imaging Therapeutic Response in Human Bone Marrow Using Rapid Whole-Body MRI

    PubMed Central

    Ballon, Douglas; Watts, Richard; Dyke, Jonathan P.; Lis, Eric; Morris, Michael J.; Scher, Howard I.; Ulug, Aziz M.; Jakubowski, Ann A.

    2008-01-01

    Whole-body imaging of therapeutic response in human bone marrow was achieved without introduced contrast agents using diffusion-weighted echo-planar magnetic resonance imaging of physiologic water. Bone marrow disease was identified relative to the strong overlying signals from water and lipids in other anatomy through selective excitation of the water resonance and generation of image contrast that was dependent upon differential nuclear relaxation times and self-diffusion coefficients. Three-dimensional displays were generated to aid image interpretation. The geometric distortion inherent in echo-planar imaging techniques was minimized through the acquisition of multiple axial slices at up to 12 anatomic stations over the entire body. Examples presented include the evaluation of therapeutic response in bone marrow during cytotoxic therapy for leukemia and metastatic prostate cancer and during cytokine administration for marrow mobilization prior to stem cell harvest. PMID:15562475

  6. Imaging therapeutic response in human bone marrow using rapid whole-body MRI.

    PubMed

    Ballon, Douglas; Watts, Richard; Dyke, Jonathan P; Lis, Eric; Morris, Michael J; Scher, Howard I; Ulu?, Aziz M; Jakubowski, Ann A

    2004-12-01

    Whole-body imaging of therapeutic response in human bone marrow was achieved without introduced contrast agents using diffusion-weighted echo-planar magnetic resonance imaging of physiologic water. Bone marrow disease was identified relative to the strong overlying signals from water and lipids in other anatomy through selective excitation of the water resonance and generation of image contrast that was dependent upon differential nuclear relaxation times and self-diffusion coefficients. Three-dimensional displays were generated to aid image interpretation. The geometric distortion inherent in echo-planar imaging techniques was minimized through the acquisition of multiple axial slices at up to 12 anatomic stations over the entire body. Examples presented include the evaluation of therapeutic response in bone marrow during cytotoxic therapy for leukemia and metastatic prostate cancer and during cytokine administration for marrow mobilization prior to stem cell harvest. PMID:15562475

  7. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  8. Aberrant cytokine signaling in leukemia

    Microsoft Academic Search

    R A Van Etten; RA Van Etten

    2007-01-01

    Abnormalities of cytokine and growth factor signaling pathways are characteristic of all forms of leukemia: lymphoid and myeloid, acute and chronic. In normal hematopoietic cells, cytokines provide the stimulus for proliferation, survival, self-renewal, differentiation and functional activation. In leukemic cells, these pathways are usurped to subserve critical parts of the malignant program. In this review, our current knowledge of leukemic

  9. Unrelated Cord Blood Transplantation after Myeloablative Conditioning in Adults with Acute Myelogenous Leukemia

    Microsoft Academic Search

    Jun Ooi; Satoshi Takahashi; Akira Tomonari; Nobuhiro Tsukada; Takaaki Konuma; Seiko Kato; Senji Kasahara; Aki Sato; Fumihiko Monma; Fumitaka Nagamura; Tohru Iseki; Arinobu Tojo; Shigetaka Asano

    2008-01-01

    We analyzed the disease-specific outcomes of adult acute myelogenous leukemia (AML) patients treated with unrelated cord blood transplantation (CBT) after myeloablative conditioning. Between August 1998 and February 2008, 77 adult patients with AML were treated with unrelated CBT. All patients received 4 fractionated 12 Gy total body irradiation (TBI) and chemotherapy as myeloablative conditioning. The median age was 45 years,

  10. Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-08

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Childhood Acute Erythroid Leukemia; Childhood Acute Megakaryoblastic Leukemia; Childhood Acute Monoblastic Leukemia; Childhood Acute Monocytic Leukemia; Childhood Acute Myeloid Leukemia With Maturation; Childhood Acute Myeloid Leukemia Without Maturation; Childhood Acute Myelomonocytic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  11. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-05

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  12. Body radiation exposure in breast cancer radiotherapy: Impact of breast IMRT and virtual wedge compensation techniques

    Microsoft Academic Search

    Tony Woo; Jean-Philippe. Pignol; Eileen Rakovitch; Toni Vu; Deanna Hicks; Peter OBrien; Kathleen Pritchard

    2006-01-01

    Purpose: Recent reports demonstrate a dramatically increased rate of secondary leukemia for breast cancer patients receiving adjuvant high-dose anthracycline and radiotherapy, and that radiation is an independent factor for the development of leukemia. This study aimed to evaluate the radiation body exposure during breast radiotherapy and to characterize the factors associated with an increased exposure. Patients and Methods: In a

  13. ORIGINAL PAPER Identifying differentially expressed genes in human acute leukemia

    E-print Network

    Gu, Xun

    ORIGINAL PAPER Identifying differentially expressed genes in human acute leukemia and mouse brain the experimental-wise false discovery rate. A human acute leukemia dataset corrected from 38 leukemia patients

  14. Genetics Home Reference: Familial acute myeloid leukemia with mutated CEBPA

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Familial acute myeloid leukemia with mutated CEBPA On this page: Description Genetic ... Reviewed May 2012 What is familial acute myeloid leukemia with mutated CEBPA? Familial acute myeloid leukemia with ...

  15. New Decision Support Tool for Acute Lymphoblastic Leukemia Classification

    E-print Network

    Chronopoulos, Anthony T.

    New Decision Support Tool for Acute Lymphoblastic Leukemia Classification Monica Madhukar affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images. Keywords: Classification

  16. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    MedlinePLUS

    ... leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is important to have frank, honest discussions ... answer many of your questions. What kind of acute lymphocytic leukemia (ALL) do I have? Do I have any ...

  17. Prognostic Factors in Childhood Leukemia (ALL or AML)

    MedlinePLUS

    ... for childhood leukemias Prognostic factors in childhood leukemia (ALL or AML) Certain factors that can affect a ... myelogenous leukemia (AML). Prognostic factors for children with ALL Children with ALL are often divided into risk ...

  18. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePLUS

    ... Topic Additional resources for chronic lymphocytic leukemia What`s new in chronic lymphocytic leukemia research and treatment? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  19. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

    ClinicalTrials.gov

    2015-06-08

    Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  20. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

    ClinicalTrials.gov

    2015-05-14

    Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  1. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  2. Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia.

    PubMed

    Studzinski, George P; Harrison, Jonathan S; Wang, Xuening; Sarkar, Surojit; Kalia, Vandana; Danilenko, Michael

    2015-08-01

    It is now well known that in the mammalian body vitamin D is converted by successive hydroxylations to 1,25-dihydroxyvitamin D (1,25D), a steroid-like hormone with pleiotropic properties. These include important contributions to the control of cell proliferation, survival and differentiation, as well as the regulation of immune responses in disease. Here, we present recent advances in current understanding of the role of 1,25D in myelopoiesis and lymphopoiesis, and the potential of 1,25D and analogs (vitamin D derivatives; VDDs) for the control of hematopoietic malignancies. The reasons for the unimpressive results of most clinical studies of the therapeutic effects of VDDs in leukemia and related diseases may include the lack of a precise rationale for the conduct of these studies. Further, clinical trials to date have generally used extremely heterogeneous patient populations and, in many cases, small numbers of patients, generally without controls. Although low calcemic VDDs have been used and combined with agents that can increase the leukemia cell killing or differentiation effects in acute leukemias, the sequencing of agents used for combination therapy should to be more clearly delineated. Most importantly, it is recommended that in future clinical trials the rationale for the basis of the enhancing action of drug combinations should be clearly articulated and the effects on anticancer immunity should also be evaluated. J. Cell. Biochem. 116: 1500-1512, 2015. © 2015 Wiley Periodicals, Inc. PMID:25694395

  3. Recognizing familial myeloid leukemia in adults

    PubMed Central

    Nickels, Eric M.; Soodalter, Jesse; Churpek, Jane E.

    2013-01-01

    Germline testing for familial cases of myeloid leukemia in adults is becoming more common with the recognition of multiple genetic syndromes predisposing people to bone marrow disease. Currently, Clinical Laboratory Improvement Amendments approved testing exists for several myeloid leukemia predisposition syndromes: familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML), caused by mutations in RUNX1; familial AML with mutated CEBPA; familial myelodysplastic syndrome and acute leukemia with mutated GATA2; and the inherited bone marrow failure syndromes, including dyskeratosis congenita, a disease of abnormal telomere maintenance. With the recognition of additional families with a genetic component to their leukemia, new predisposition alleles will likely be identified. We highlight how to recognize and manage these cases as well as outline the characteristics of the major known syndromes. We look forward to future research increasing our understanding of the scope of inherited myeloid leukemia syndromes. PMID:23926458

  4. Electron tomography of fiber cell cytoplasm and dense cores of multilamellar bodies from human age-related nuclear cataracts

    E-print Network

    Johnsen, Sönke

    of the lens (Costello and Kuszak, 2008; Graw, 2009; Michael and Bron, 2011; Zhou et al., 2011). The entire-related nuclear cataracts M. Joseph Costello a,*, Alain Burette a , Mariko Weber a , Sangeetha Metlapally a , Kurt-Ghoul et al., 1996; Costello et al., 2008; Vre

  5. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2013-07-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  6. Establishment and testing of a whole body counter for the Texas A&M Nuclear Science Center 

    E-print Network

    Baca, Bernadette Doris

    1997-01-01

    deviation using the whole body counter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Comparison between HPGe and NaI performance testing activities. . 39 Comparison of the calculated average MDAs and associated nuclide ALI... with similar energies, the different energy events of the radiation within the crystal are seen as the same energy because of the poor resolution (Knoll 19g9). Deciphering a majority of the identifying or key gamma rays for individual nuclides can be a...

  7. Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human

    Microsoft Academic Search

    Duong P. Huynh; Karla Figueroa; Nam Hoang; Stefan-M. Pulst

    2000-01-01

    Instability of CAG DNA trinucleotide repeats is the mutational mechanism for several neurodegenerative diseases resulting in the expansion of a polyglutamine (polyQ) tract. Proteins with long polyQ tracts have an increased tendency to aggregate, often as truncated fragments forming ubiquitinated intranuclear inclusion bodies. We examined whether similar features define spinocerebellar ataxia type 2 (SCA2) pathogenesis using cultured cells, human brains

  8. Rituximab in chronic lymphocytic leukemia.

    PubMed

    James, Danelle F; Kipps, Thomas J

    2011-07-01

    Rituximab (Rituxan; iogen Idec, San Diego, CA, USA) is a human-mouse chimeric monoclonal antibody specific for CD20, a surface glycoprotein expressed on B lymphocytes. Administration of rituximab as a single agent to patients with chronic lymphocytic leukemia (CLL) has limited clinical activity, but generally does not eradicate leukemia from the marrow. However, when administered in combination with chemotherapy, rituximab can improve the survival of patients relative to those treated with chemotherapy alone. As a result of this, the US Food and Drug Administration approved the use of rituximab in previously untreated and previously treated CD20-positive CLL in combination with fludarabine monophosphate and cyclophosphamide. The results of clinical studies evaluating the activity of rituximab when used alone or in combination with other antileukemia agents for the treatment of this disease are reviewed here. PMID:21725721

  9. Protective effects of nuclear factor erythroid 2-related factor 2 on whole body heat stress-induced oxidative damage in the mouse testis

    PubMed Central

    2013-01-01

    Background Whole body heat stress had detrimental effect on male reproductive function. It's known that the nuclear factor erythroid 2-related factor 2 (Nrf2) activates expression of cytoprotective genes to enable cell adaptation to protect against oxidative stress. However, it’s still unclear about the exactly effects of Nrf2 on the testis. Here, we investigate the protective effect of Nrf2 on whole body heat stress-induced oxidative damage in mouse testis. Methods Male mice were exposed to the elevated ambient temperature (42°C) daily for 2 h. During the period of twelve consecutive days, mice were sacrificed on days 1, 2, 4, 8 and 12 immediately following heat exposure. Testes weight, enzymatic antioxidant activities and concentrations of malondialdehyde (MDA) and glutathione (GSH) in the testes were determined and immunohistochemical detection of Nrf2 protein and mRNA expression of Nrf2-regulated genes were analyzed to assess the status of Nrf2-antioxidant system. Results Heat-exposed mice presented significant increases in rectal, scrotal surface and body surface temperature. The concentrations of cortisol and testosterone in serum fluctuated with the number of exposed days. There were significant decrease in testes weight and relative testes weight on day 12 compared with those on other days, but significant increases in catalase (CAT) activity on day 1 and GSH level on day 4 compared with control group. The activities of total superoxide dismutase (T-SOD) and copper-zinc SOD (CuZn-SOD) increased significantly on days 8 and 12. Moreover, prominent nuclear accumulation of Nrf2 protein was observed in Leydig cells on day 2, accompanying with up-regulated mRNA levels of Nrf2-regulated genes such as Nrf2, heme oxygenase 1 (HO-1), ?-Glutamylcysteine synthetase (GCLC) and NAD (P) H: quinone oxidoreductase 1 (NQO1)) in heat-treated groups. Conclusions These results suggest that Nrf2 displayed nuclear accumulation and protective activity in the process of heat treated-induced oxidative stress in mouse testes, indicating that Nrf2 might be a potential target for new drugs designed to protect germ cell and Leydig cell from oxidative stress. PMID:23514035

  10. Diagnosis of Acute Lymphoblastic Leukemia

    Microsoft Academic Search

    Maher Albitar; Francis J. Giles; Hagop Kantarjian

    The diagnosis of acute lymphoblastic leukemia (ALL) is dependent on the identification and characterization of blast cells\\u000a in peripheral blood or bone marrow. Although it is not clear why blasts have a tendency to circulate in some patients and\\u000a not in others, ALL can be reliably diagnosed using peripheral blood or bone marrow blasts when blasts are in circulation [79].

  11. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

    SciTech Connect

    Garcia, C.C. [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina)] [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina); Topisirovic, I. [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada)] [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada); Djavani, M. [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States)] [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States); Borden, K.L.B. [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada)] [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada); Damonte, E.B. [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina)] [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina); Salvato, M.S., E-mail: msalvato@ihv.umaryland.edu [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States)

    2010-03-19

    The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

  12. Chronic basophilic leukemia: a rare form of chronic myeloproliferative neoplasm.

    PubMed

    Tang, Guilin; Woods, Lesley J; Wang, Sa A; Brettler, Doreen; Andersen, Mary; Miron, Patricia M; Pechet, Liberto; Woda, Bruce A; Hao, Suyang

    2009-08-01

    Chronic basophilic leukemia is a rare and poorly characterized entity. Only a limited number of cases have been described. Herein, we report a patient who presented with fatigue, weight loss, leukocytosis, persistent prominent basophilia, and mild eosinophilia. The bone marrow showed features characteristic of a myeloproliferative neoplasm with a marked increase in maturing basophils. The basophils exhibited nuclear hypersegmentation, abnormal granulation, and abnormally low CD38 expression. Conventional karyotyping revealed a t(5;12)(q31;p13). ETV6 but not PDGFRB rearrangement was detected by fluorescence in situ hybridization. PMID:19427022

  13. Ultrastructure of adult T-cell leukemia\\/lymphoma

    Microsoft Academic Search

    Tadaaki Eimoto; Tetsuji Mitsui; Masahiro Kikuchi

    1981-01-01

    Summary  Eighteen cases of adult T-cell leukemia\\/lymphoma (ATLL) in Japan were analyzed by electron microscopy and compared with 5\\u000a cases of B-lymphoma and well-established groups of T-lymphomas (4 cases of T-lymphoblastic lymphoma and 2 cases of Sézary\\u000a syndrome). Five hundred cells in each case, categorized ultrastructurally as to the cellular size and nuclear shape, showed\\u000a an essentially pleomorphic cellular distribution in

  14. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    PubMed

    Topka, Sabine; Vijai, Joseph; Walsh, Michael F; Jacobs, Lauren; Maria, Ann; Villano, Danylo; Gaddam, Pragna; Wu, Gang; McGee, Rose B; Quinn, Emily; Inaba, Hiroto; Hartford, Christine; Pui, Ching-Hon; Pappo, Alberto; Edmonson, Michael; Zhang, Michael Y; Stepensky, Polina; Steinherz, Peter; Schrader, Kasmintan; Lincoln, Anne; Bussel, James; Lipkin, Steve M; Goldgur, Yehuda; Harit, Mira; Stadler, Zsofia K; Mullighan, Charles; Weintraub, Michael; Shimamura, Akiko; Zhang, Jinghui; Downing, James R; Nichols, Kim E; Offit, Kenneth

    2015-06-01

    Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition. PMID:26102509

  15. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia

    PubMed Central

    Jacobs, Lauren; Maria, Ann; Villano, Danylo; Gaddam, Pragna; Wu, Gang; McGee, Rose B.; Quinn, Emily; Inaba, Hiroto; Hartford, Christine; Pui, Ching-hon; Pappo, Alberto; Edmonson, Michael; Zhang, Michael Y.; Stepensky, Polina; Steinherz, Peter; Schrader, Kasmintan; Lincoln, Anne; Bussel, James; Lipkin, Steve M.; Goldgur, Yehuda; Harit, Mira; Stadler, Zsofia K.; Mullighan, Charles; Weintraub, Michael; Shimamura, Akiko; Zhang, Jinghui; Downing, James R.; Nichols, Kim E.; Offit, Kenneth

    2015-01-01

    Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition. PMID:26102509

  16. Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-04-08

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Deuterium enrichment of plasma determined by nuclear magnetic resonance spectroscopy: Dilution kinetics of sup 2 H sub 2 O and estimation of total body water

    SciTech Connect

    Brans, Y.W.; Schwartz, C.A.; Hood, R.J.; Ksebati, M.B.; Konduri, G.G. (Wayne State Univ., Detroit, MI (USA))

    1990-10-01

    We demonstrate the feasibility of quantifying the abundance of {sup 2}H in plasma by nuclear magnetic resonance (NMR) spectroscopy. After adding internal standard (tert-butyl-d9 alcohol) to deproteinized plasma samples containing {sup 2}H{sub 2}O, we determined the ratio of NMR peak areas for {sup 2}H{sub 2}O and tert-butyl-d9 alcohol. This peak-area ratio was directly proportional to the exogenous {sup 2}H enrichment of plasma (difference between measured and naturally occurring {sup 2}H) between 0 and 0.272 atom % (r = 0.999). The coefficient of variation was 1.34% at an exogenous enrichment of 0.136 atom %. We applied this method to a study of the dilution kinetics of {sup 2}H{sub 2}O to determine the optimal time and method of blood sampling for estimation of total body water content. The {sup 2}H enrichment of plasma stabilized by 4 h after intravenous injection of {sup 2}H{sub 2}O, 1 g/kg of body weight, and fluctuated within 2-4% of the 4- to 8-h mean thereafter.

  18. Two Critical Hits for Promyelocytic Leukemia

    Microsoft Academic Search

    Li-Zhen He; Mantu Bhaumik; Carla Tribioli; Eduardo M Rego; Sarah Ivins; Arthur Zelent; Pier Paolo Pandolfi

    2000-01-01

    Acute promyelocytic leukemia (APL) is associated with chromosomal translocations that always involve the RAR? gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes). Due to the reciprocity of the translocation, X-RAR ? and RAR ?-X fusion proteins coexist in APL blasts. PLZF-RAR? transgenic mice (TM) develop leukemia that lacks the differentiation block at

  19. Advances in treating chronic lymphocytic leukemia

    PubMed Central

    Tausch, Eugen; Mertens, Daniel

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia, affects mostly elderly CLL patients, and is incurable without allogeneic transplantation. Although classic chemo(immuno)therapy is still the standard of care for patients in need of treatment, this paradigm might change in the near future with the advent of new therapeutic agents targeting major pathogenic pathways in CLL. PMID:25165564

  20. ORIGINAL ARTICLE Molecular recognition of acute myeloid leukemia using aptamers

    E-print Network

    Tan, Weihong

    ORIGINAL ARTICLE Molecular recognition of acute myeloid leukemia using aptamers K Sefah1,2 , ZW live acute myeloid leukemia (AML) cells to select a group of DNA aptamers, which can recognize AML molecular analysis of leukemia and its subcategories. Leukemia (2009) 23, 235­244; doi:10.1038/leu.2008

  1. Trisomy 13: A New Recurring Chromosome Abnormality in Acute Leukemia

    Microsoft Academic Search

    Hartmut Dohner; Diane C. Arthur; Edward D. Ball; Robert E. Sobol; Frederick R. Davey; David Lawrence; Lawrence Gordon; Shivanand R. Patil; Rawatmal B. Surana; Joseph R. Testa; Ram S. Verma; Charles A. Schiffer; Doris H. Wurster-Hill; Clara D. Bloomfield

    1990-01-01

    A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morpho- logic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and my- eloid leukemia, one as acute lymphoid leukemia,

  2. Veliparib and Temozolomide in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2015-05-22

    Accelerated Phase of Disease; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams

    SciTech Connect

    Kanematsu, Nobuyuki; Inaniwa, Taku; Koba, Yusuke [Department of Accelerator and Medical Physics, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2012-02-15

    Purpose: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction. Methods: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction. Results: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone. Conclusions: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user's specific system.

  4. Phytochrome B Nuclear Bodies Respond to the Low Red to Far-Red Ratio and to the Reduced Irradiance of Canopy Shade in Arabidopsis1[C][W][OPEN

    PubMed Central

    Trupkin, Santiago Ariel; Legris, Martina; Buchovsky, Ana Sabrina; Tolava Rivero, María Belén; Casal, Jorge José

    2014-01-01

    The current consensus is that plant responses to canopy shade involve the perception of low red to far-red ratios (R:FRs) by phytochrome B (phyB), which leads to the direct activation of auxin synthesis genes by PHYTOCHROME INTERACTING FACTORs (PIFs). In addition to its effect on R:FRs, shade also reduces irradiance, but whether shade-induced drops in irradiance affect phyB activity has not been demonstrated. To address this issue, we investigated whether irradiance and R:FRs have similar effects on the nuclear distribution of phyB in petiole cells of light-grown plants. Under high-irradiance white light, phyB formed large nuclear bodies. Lowering irradiance without changing R:FRs or lowering R:FRs by adding far-red light led to the appearance of small nuclear bodies containing phyB. Large nuclear bodies remained but with some concomitant reduction in diameter. The appearance of small nuclear bodies was rapid, stable, and reversible upon the return to high irradiance and high R:FRs. High levels of red light but not of blue light were enough to restrain the formation of small phyB nuclear bodies. Irradiance was effective within the range found in natural canopies and even under relatively low R:FRs. The promotion of leaf hyponasty by lowering irradiance was impaired in phyB and pif mutants, as previously reported for the response to R:FRs. The expression of auxin-related genes showed a similar hierarchy of response to low R:FRs and low irradiance. We propose that phyB is able to perceive not only the low R:FRs, but also the low irradiance of shade. PMID:24948827

  5. Many-body correlations of quasiparticle random-phase approximation in nuclear matrix element of neutrinoless double-beta decay

    E-print Network

    J. Terasaki

    2015-01-19

    We show that the correlations of the quasiparticle random-phase approximation (QRPA) significantly reduce the nuclear matrix element (NME) of neutrinoless double-beta decay by a new mechanism in the calculation for $^{150}$Nd $\\rightarrow$ $^{150}$Sm. This effect is due mainly to the normalization factors of the QRPA ground states included in the overlap of intermediate states, to which the QRPA states based on the initial and final ground states are applied. These normalization factors arise according to the definition of the QRPA ground state as the vacuum of quasibosons. Our NME is close to those of other groups in spite of this new reduction effect because we do not use the proton-neutron pairing interaction usually used for reproducing the experimental NME of the two-neutrino double-beta ($2\

  6. Preliminary experimental results in humans and animals with a superconducting, whole-body, nuclear magnetic resonance scanner. [Dogs

    SciTech Connect

    Alfidi, R.J, (Case Western Reserve Univ., Cleveland, OH); Haaga, J.R.; El Yousef, S.J.

    1982-04-01

    In order to determine the clinical usefulness of nuclear magnetic resonance (NMR) imaging, the investigators examined a variety of normal volunteers, patients with neoplastic lesions, and experimental animals. Preliminary results were obtained with the use of potential contrast agents. It was found that imaging applications of NMR in the vascular system, spine, brain, lung, and mediastinum offer certain advantages over other modalities. The absence of biological hazard as well as the ability to obtain unenhanced, noninvasive, gated images of the vascular system, as demonstrated in this study, make NMR particularly attractive. In addition to single-section capability, NMR makes it possible to obtain volume images of the spine and other organs which can be displayed in any desired plane or section thickness.

  7. Biosampling Case Children with Leukemia (Acute Lymphocytic and Myelocytic Leukemia) and a Reference Population in Sierra Vista, Arizona

    E-print Network

    Biosampling Case Children with Leukemia (Acute Lymphocytic and Myelocytic Leukemia) and a Reference. Statistical methods E. Investigation Protocol, Biosampling of case Children with Leukemia (Acute Lymphocytic and Acute Myelocytic Leukemia) and a Reference Population in Sierra Vista, Arizona 2 #12;Tables 1. Selected

  8. Asparaginase in acute lymphoblastic leukemia.

    PubMed

    Kawedia, Jitesh D; Rytting, Michael E

    2014-09-01

    Cure rates in pediatric acute lymphoblastic leukemia have significantly improved over the past decades. Now, almost 90% of children will survive the disease. The cure rates in adolescents, young adults, and adults have not kept pace with the improvements in younger patients, even though almost an equal proportion of adult patients achieve complete remission as their pediatric counterparts. Differences in treatment regimens might be important. Intensive use of asparaginase has been a key component of successful pediatric therapy. In this review, we focus on the use of asparaginase and the potential of optimizing asparaginase use via monitoring to minimize adverse drug events and improve efficacy of the drug. PMID:25486949

  9. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Many-body correlations of quasiparticle random-phase approximation in nuclear matrix elements of neutrinoless double-? decay

    NASA Astrophysics Data System (ADS)

    Terasaki, J.

    2015-03-01

    We show that the correlations of the quasiparticle random-phase approximation (QRPA) significantly reduce the nuclear matrix element (NME) of neutrinoless double-? decay by a new mechanism in the calculation for 150Nd?150Sm. This effect is due mainly to the normalization factors of the QRPA ground states included in the overlap of intermediate states, to which the QRPA states based on the initial and final ground states are applied. These normalization factors arise according to the definition of the QRPA ground state as the vacuum of quasibosons. Our NME is close to those of other groups in spite of this new reduction effect because we do not use the proton-neutron pairing interaction that is usually used for reproducing the experimental NME of the two-neutrino double-? (2 ? ? ? ) decay, without those normalization factors, and reduces the NME appreciably. Our method can reproduce the experimental 2 ? ? ? NME for 150Nd?150Sm with the quenching axial-vector current coupling without approaching the breaking point of the QRPA. The consistency of QRPA approaches taking different virtual paths under the closure approximation is also discussed, and an extension of the QRPA ground state is proposed.

  11. Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

    PubMed Central

    Gallina, Irene; Colding, Camilla; Henriksen, Peter; Beli, Petra; Nakamura, Kyosuke; Offman, Judith; Mathiasen, David P.; Silva, Sonia; Hoffmann, Eva; Groth, Anja; Choudhary, Chunaram; Lisby, Michael

    2015-01-01

    DNA replication stress is a source of genomic instability. Here we identify changed mutation rate 1 (Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that Cmr1—together with Mrc1/Claspin, Pph3, the chaperonin containing TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to Cmr1, its human orthologue WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that Cmr1/WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins. PMID:25817432

  12. Analysis of Wilms tumor gene (WT1) expression in acute leukemia patients with special reference to the differential diagnosis between eosinophilic leukemia and idiopathic hypereosinophilic syndromes.

    PubMed

    Menssen, H D; Schmidt, A; Bartelt, S; Arjomand, A; Thomsen, H; Leben, R; Kath, R; Thiel, E

    2000-01-01

    Continuous Wilms' tumor gene (WT1) expression is a typical feature of leukemic blasts in AML, ALL, and blast crisis CML patients. It is easily detectable by a variety of RT-PCR protocols, which differ mainly in their sensitivity. The nuclear WT1 protein can be found in blasts of approximately 50-60% of acute leukemia patients at diagnosis. Conversely, WT1 is only transiently expressed in normal hemopoiesis. Early CD34+ hemopoietic progenitors express WT1, whereas no WT1 mRNA transcripts can be found in mature blood cells and differentiation-induced committed CD34- progenitors. As a powerful complementary diagnostic tool, testing for WT1 expression can be helpful to discriminate between eosinophilic leukemia (EoL) patients and patients with idiopathic hypereosinophilic syndromes. Conflicting data about the usefulness of testing for WT1 expression to monitor minimal residual disease (MRD) in treated leukemia patients will be discussed. Finally, research strategies to circumvent shortcomings in detecting leukemia-associated WT1 expression will be outlined. PMID:10674900

  13. Therapeutic use of fractionated total body and subtotal body irradiation. [X-rays

    SciTech Connect

    Loeffler, R.K.

    1981-05-01

    Ninety-one patients were treated using fractionated subtotal body (STBI) or total body irradiation (TBI). These patients had generalized lymphomas, Hodgkin's disease, leukemias, myelomas, seminomas, or oat-cell carcinomas. Subtotal body irradiation is delivered to the entire body, except for the skull and extremities. It was expected that a significantly higher radiation dose could be administered with STBI than with TBI. A five- to ten-fold increase in tolerance for STBI was demonstrated. Many of these patients have had long-term emissions. There is little or no treatment-induced symptomatology, and no sanctuary sites.

  14. Immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G

    2005-09-01

    Immunotherapeutic strategies have become part of standard cancer treatment. Chimeric and humanized antibodies have demonstrated activity against a variety of tumors. Although the humanized anti-CD33 antibody HuM195 has only modest activity against overt acute myeloid leukemia (AML), it can eliminate minimal residual disease in acute promyelocytic leukemia. High-dose radioimmunotherapy with b-particle-emitting isotopes targeting CD33, CD45, and CD66 can potentially allow intensification of antileukemic therapy before hematopoietic stem cell transplantation. Conversely, a-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumor cell kill while sparing surrounding normal tissues. Targeted chemotherapy with the anti-CD33- calicheamicin construct gemtuzumab ozogamicin has produced remissions in relapsed AML and appears promising when used in combination with standard chemotherapy for newly diagnosed AML. T-cell recognition of peptide antigens presented on the cell surface in combination with major histocompatibility complex antigen provides another potentially promising approach for the treatment of AML. PMID:16091194

  15. A fraction of neurofibromin interacts with PML bodies in the nucleus of the CCF astrocytoma cell line

    SciTech Connect

    Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice; Doudeau, Michel; Morisset-Lopez, Severine [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)] [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Ardourel, Maryvonne; Hevor, Tobias [Laboratoire de Neurobiologie, Universite d'Orleans, BP 6759, 45067 Orleans Cedex 2 (France)] [Laboratoire de Neurobiologie, Universite d'Orleans, BP 6759, 45067 Orleans Cedex 2 (France); Pichon, Chantal [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)] [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Benedetti, Helene, E-mail: helene.benedetti@cnrs-orleans.fr [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)] [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d'Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer We validate the use of specific anti-Nf1 antibodies for immunofluorescence studies. Black-Right-Pointing-Pointer We detect Nf1 in the cytoplasm and nucleus of CCF cells. Black-Right-Pointing-Pointer We demonstrate that Nf1 partially colocalizes with PML nuclear bodies. Black-Right-Pointing-Pointer We demonstrate that there is a direct interaction between a fraction of Nf1 and the PML bodies. -- Abstract: Neurofibromatosis type 1 is a common genetic disease that causes nervous system tumors, and cognitive deficits. It is due to mutations within the NF1 gene, which encodes the Nf1 protein. Nf1 has been shown to be involved in the regulation of Ras, cAMP and actin cytoskeleton dynamics. In this study, using immunofluorescence experiments, we have shown a partial nuclear localization of Nf1 in the astrocytoma cell line: CCF and we have demonstrated that Nf1 partially colocalizes with PML (promyelocytic leukemia) nuclear bodies. A direct interaction between Nf1 and the multiprotein complex has further been demonstrated using 'in situ' proximity ligation assay (PLA).

  16. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-29

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-01

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Small Molecule that Reverses Dexamethasone Resistance in Tcell Acute Lymphoblastic Leukemia (T-ALL)

    E-print Network

    Stockwell, Brent R.

    Small Molecule that Reverses Dexamethasone Resistance in Tcell Acute Lymphoblastic Leukemia (T are one of the most utilized and effective therapies in treating T-cell acute lymphoblastic leukemia lymphoblastic leukemia, dexamethasone, glucocorticoid resistance, NOTCH1 Acute lymphoblastic leukemia (ALL

  19. S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-25

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  1. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-25

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. 5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-10-09

    Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  3. S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2015-03-05

    Acute Leukemias of Ambiguous Lineage; B-cell Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma

  4. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-02-10

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  5. Reproducibility and accuracy of body composition assessments in mice by dual energy x-ray absorptiometry and time domain nuclear magnetic resonance

    PubMed Central

    Halldorsdottir, Solveig; Carmody, Jill; Boozer, Carol N.; Leduc, Charles A.; Leibel, Rudolph L.

    2011-01-01

    Objective To assess the accuracy and reproducibility of dual-energy absorptiometry (DXA; PIXImus™) and time domain nuclear magnetic resonance (TD-NMR; Bruker Optics) for the measurement of body composition of lean and obese mice. Subjects and measurements Thirty lean and obese mice (body weight range 19–67 g) were studied. Coefficients of variation for repeated (x 4) DXA and NMR scans of mice were calculated to assess reproducibility. Accuracy was assessed by comparing DXA and NMR results of ten mice to chemical carcass analyses. Accuracy of the respective techniques was also assessed by comparing DXA and NMR results obtained with ground meat samples to chemical analyses. Repeated scans of 10–25 gram samples were performed to test the sensitivity of the DXA and NMR methods to variation in sample mass. Results In mice, DXA and NMR reproducibility measures were similar for fat tissue mass (FTM) (DXA coefficient of variation [CV]=2.3%; and NMR CV=2.8%) (P=0.47), while reproducibility of lean tissue mass (LTM) estimates were better for DXA (1.0%) than NMR (2.2%) (

    body composition lean and obese mice. While DXA and NMR measures are highly correlated with chemical analysis measures, DXA consistently overestimates LTM and FTM (by ~8% and ~46%, respectively), while NMR only slightly underestimates LTM (by ~0.2%) and overestimates FTM (~15%.) The NMR method also has practical advantages compared to DXA, such as speed of measurement and the ability to scan unanesthetized animals. PMID:21909234

  6. Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-14

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Accurate and rapid docking of protein–protein complexes on the basis of intermolecular nuclear Overhauser enhancement data and dipolar couplings by rigid body minimization

    PubMed Central

    Clore, G. Marius

    2000-01-01

    A simple and rapid method is presented for solving the three-dimensional structures of protein–protein complexes in solution on the basis of experimental NMR restraints that provide the requisite translational (i.e., intermolecular nuclear Overhauser enhancement, NOE, data) and orientational (i.e., backbone 1H-15N dipolar couplings and intermolecular NOEs) information. Providing high-resolution structures of the proteins in the unbound state are available and no significant backbone conformational changes occur upon complexation (which can readily be assessed by analysis of dipolar couplings measured on the complex), accurate and rapid docking of the two proteins can be achieved. The method, which is demonstrated for the 40-kDa complex of enzyme I and the histidine phosphocarrier protein, involves the application of rigid body minimization using a target function comprising only three terms, namely experimental NOE-derived intermolecular interproton distance and dipolar coupling restraints, and a simple intermolecular van der Waals repulsion potential. This approach promises to dramatically reduce the amount of time and effort required to solve the structures of protein–protein complexes by NMR, and to extend the capabilities of NMR to larger protein–protein complexes, possibly up to molecular masses of 100 kDa or more. PMID:10922057

  8. Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies

    PubMed Central

    Kariya, Shingo; Re, Diane B.; Jacquier, Arnaud; Nelson, Katelyn; Przedborski, Serge; Monani, Umrao R.

    2012-01-01

    Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among the most common motor neuron diseases to afflict the human population. A deficiency of the survival of motor neuron (SMN) protein causes SMA and is also reported to be an exacerbating factor in the development of ALS. However, pathways linking the two diseases have yet to be defined and it is not clear precisely how the pathology of ALS is aggravated by reduced SMN or whether mutant proteins underlying familial forms of ALS interfere with SMN-related biochemical pathways to exacerbate the neurodegenerative process. In this study, we show that mutant superoxide dismutase-1 (SOD1), a cause of familial ALS, profoundly alters the sub-cellular localization of the SMN protein, preventing the formation of nuclear ‘gems’ by disrupting the recruitment of the protein to Cajal bodies. Overexpressing the SMN protein in mutant SOD1 mice, a model of familial ALS, alleviates this phenomenon, most likely in a cell-autonomous manner, and significantly mitigates the loss of motor neurons in the spinal cord and in culture dishes. In the mice, the onset of the neuromuscular phenotype is delayed and motor function enhanced, suggestive of a therapeutic benefit for ALS patients treated with agents that augment the SMN protein. Nevertheless, this finding is tempered by an inability to prolong survival, a limitation most likely imposed by the inexorable denervation that characterizes ALS and eventually disrupts the neuromuscular synapses even in the presence of increased SMN. PMID:22581780

  9. Assessment of internal exposure doses in Fukushima by a whole body counter within one month after the nuclear power plant accident.

    PubMed

    Matsuda, Naoki; Kumagai, Atsushi; Ohtsuru, Akira; Morita, Naoko; Miura, Miwa; Yoshida, Masahiro; Kudo, Takashi; Takamura, Noboru; Yamashita, Shunichi

    2013-06-01

    Information on early internal radiation doses in Fukushima after the nuclear power plant accident on March 11, 2011, is quite limited due to initial organizational difficulties, high background radiation and contamination of radiation measuring devices. In Nagasaki, approximately 1,200 km away from Fukushima, the internal radioactivity in evacuees and short-term visitors to Fukushima has been measured by a whole body counter (WBC) since March 15, 2011. A horizontal bed-type scanning WBC equipped with two NaI(Tl) scintillation detectors was used for 173 people who stayed in the Fukushima prefecture between March 11 and April 10, 2011. The average length of stay was 4.8 days. The internal radioactivity was converted to an estimated amount of intake according to the scenario of acute inhalation, and then the committed effective dose and the thyroid dose were evaluated. (131)I, (134)Cs and (137)Cs were detected in more than 30% of examined individuals. In subjects who stayed in Fukushima from March 12 to March 18, the detection rate was approximately 50% higher for each radionuclide and 44% higher for all three nuclides. The maximum committed effective dose and thyroid equivalent dose were 1 mSv and 20 mSv, respectively. Although the number of subjects and settlements in the study are limited, the results suggest that the internal radiation exposure in Fukushima due to the intake of radioactive materials shortly after the accident will probably not result in any deterministic or stochastic health effects. PMID:23642080

  10. Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies and regulation of p53

    SciTech Connect

    Sung, Ki Sa; Lee, Yun-Ah [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)] [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, Eui Tae [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Seung-Rock [Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190 (Korea, Republic of)] [Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190 (Korea, Republic of); Ahn, Jin-Hyun [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)] [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Choi, Cheol Yong, E-mail: choicy@skku.ac.kr [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2011-04-15

    Homeodomain-interacting protein kinase 2 (HIPK2) is a key regulator of various transcription factors including p53 and CtBP in the DNA damage signaling pathway. PML-nuclear body (NB) is required for HIPK2-mediated p53 phosphorylation at Ser46 and induction of apoptosis. Although PML-NB targeting of HIPK2 has been shown, much is not clear about the molecular mechanism of HIPK2 recruitment to PML-NBs. Here we show that HIPK2 colocalizes specifically with PML-I and PML-IV. Mutational analysis showed that HIPK2 recruitment to PML-IV-NBs is mediated by the SUMO-interaction motifs (SIMs) of both PML-IV and HIPK2. Wild-type HIPK2 associated with SUMO-conjugated PML-IV at a higher affinity than with un-conjugated PML-IV, while the association of a HIPK2 SIM mutant with SUMO-modified PML-IV was impaired. In colony formation assays, HIPK2 strongly suppressed cell proliferation, but HIPK2 SIM mutants did not. In addition, activation and phosphorylation of p53 at the Ser46 residue were impaired by HIPK2 SIM mutants. These results suggest that SIM-mediated HIPK2 targeting to PML-NBs is crucial for HIPK2-mediated p53 activation and induction of apoptosis.

  11. Empowering Preadolescent and Adolescent Leukemia Patients.

    ERIC Educational Resources Information Center

    Price, Kathy

    1988-01-01

    Describes effects of leukemia diagnosis and treatment for preadolescents and adolescents. Discusses strategies for social workers to assist these cancer patients in participating actively in the day-to-day management of their own care. (ABL)

  12. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePLUS

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  13. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    MedlinePLUS

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  14. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePLUS

    ... 2 treatment phases of adult AML are: Remission induction therapy : This is the first phase of treatment. ... adult acute myeloid leukemia (AML) during the remission induction phase depends on the subtype of AML and ...

  15. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    MedlinePLUS

    ... is made mostly of fat. Leukemia may affect red blood cells, white blood cells, and platelets. Normally, ... one of three types of mature blood cells: Red blood cells that carry oxygen and other substances ...

  16. Treatment Options for Hairy Cell Leukemia

    MedlinePLUS

    ... is made mostly of fat. Leukemia may affect red blood cells, white blood cells, and platelets. Normally, ... one of three types of mature blood cells: Red blood cells that carry oxygen and other substances ...

  17. Treatment Options for Chronic Myelogenous Leukemia

    MedlinePLUS

    ... is made mostly of fat. Leukemia may affect red blood cells, white blood cells, and platelets. Normally, ... one of three types of mature blood cells: Red blood cells that carry oxygen and other substances ...

  18. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePLUS

    ... type of cancer in children. Leukemia may affect red blood cells, white blood cells, and platelets. In ... one of three types of mature blood cells: Red blood cells that carry oxygen and other substances ...

  19. Therapeutically Targetable ALK Mutations in Leukemia.

    PubMed

    Maxson, Julia E; Davare, Monika A; Luty, Samuel B; Eide, Christopher A; Chang, Bill H; Loriaux, Marc M; Tognon, Cristina E; Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K; Druker, Brian J; Tyner, Jeffrey W

    2015-06-01

    Genome sequencing is revealing a vast mutational landscape in leukemia, offering new opportunities for treatment with targeted therapy. Here, we identify two patients with acute myelogenous leukemia and B-cell acute lymphoblastic leukemia whose tumors harbor point mutations in the ALK kinase. The mutations reside in the extracellular domain of ALK and are potently transforming in cytokine-independent cellular assays and primary mouse bone marrow colony formation studies. Strikingly, both mutations conferred sensitivity to ALK kinase inhibitors, including the FDA-approved drug crizotinib. On the basis of our results, we propose that tumors harboring ALK mutations may be therapeutically tractable for personalized treatment of certain aggressive leukemias with ALK inhibitors. Cancer Res; 75(11); 2146-50. ©2015 AACR. PMID:26032424

  20. Temporal changes in water quality at a childhood leukemia cluster

    USGS Publications Warehouse

    Seiler, R.L.

    2004-01-01

    Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter progeny is attained in pressure tanks overnight.

  1. Temporal changes in water quality at a childhood leukemia cluster.

    PubMed

    Seiler, Ralph L

    2004-01-01

    Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter progeny is attained in pressure tanks overnight. PMID:15161161

  2. Childhood Leukemia--A Look at the Past, the Present and the Future.

    ERIC Educational Resources Information Center

    Findeisen, Regina; Barber, William H.

    1997-01-01

    Provides an overview of childhood leukemia. The causes, the survival period, different types (acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and hairy cell leukemia), symptoms, treatment, side effects of treatment (including learning problems), and the expected future direction of…

  3. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2014-09-30

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  5. Inhibition of STAT5: A therapeutic option in BCR-ABL1-driven leukemia

    PubMed Central

    Berger, Angelika; Sexl, Veronika; Valent, Peter; Moriggl, Richard

    2014-01-01

    The two transcription factors STAT5A and STAT5B are central signaling molecules in leukemias driven by Abelson fusion tyrosine kinases and they fulfill all criteria of drug targets. STAT5A and STAT5B display unique nuclear shuttling mechanisms and they have a key role in resistance of leukemic cells against treatment with tyrosine kinase inhibitors (TKI). Moreover, STAT5A and STAT5B promote survival of leukemic stem cells. We here discuss the possibility of targeting up-stream kinases with TKI, direct STAT5 inhibition via SH2 domain obstruction and blocking nuclear translocation of STAT5. All discussed options will result in a stop of STAT5 transport to the nucleus to block STAT5-mediated transcriptional activity. In summary, recently described shuttling functions of STAT5 are discussed as potentially druggable pathways in leukemias. PMID:25333255

  6. Acute Myeloid Leukemia, Version 2.2013

    PubMed Central

    O'Donnell, Margaret R.; Tallman, Martin S.; Abboud, Camille N.; Altman, Jessica K.; Appelbaum, Frederick R.; Arber, Daniel A.; Attar, Eyal; Borate, Uma; Coutre, Steven E.; Damon, Lloyd E.; Lancet, Jeffrey; Maness, Lori J.; Marcucci, Guido; Martin, Michael G.; Millenson, Michael M.; Moore, Joseph O.; Ravandi, Farhad; Shami, Paul J.; Smith, B. Douglas; Stone, Richard M.; Strickland, Stephen A.; Wang, Eunice S.; Gregory, Kristina M.; Naganuma, Maoko

    2014-01-01

    These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that support the recommendations. The updates described in this article focus on the acute promyelocytic leukemia (APL) section, featuring recommendations for additional induction/consolidation regimens in patients with low- or intermediate-risk APL, and providing guidance on maintenance strategies for APL. PMID:24029121

  7. Acute Myeloid Leukemia | Office of Cancer Genomics

    Cancer.gov

    Acute myeloid leukemia (AML) is a cancer that originates in the bone marrow from immature white blood cells known as myeloblasts. About 25% of all children with leukemia have AML. Although survival rates have increased since the 1970s, approximately half of all childhood AML cases relapse despite intensive treatment. Additional therapies following relapse are often unsuccessful and can be especially difficult and damaging for children. These patients would clearly benefit from targeted therapeutic approaches.

  8. Acute myeloid leukemia, version 2.2013.

    PubMed

    O'Donnell, Margaret R; Tallman, Martin S; Abboud, Camille N; Altman, Jessica K; Appelbaum, Frederick R; Arber, Daniel A; Attar, Eyal; Borate, Uma; Coutre, Steven E; Damon, Lloyd E; Lancet, Jeffrey; Maness, Lori J; Marcucci, Guido; Martin, Michael G; Millenson, Michael M; Moore, Joseph O; Ravandi, Farhad; Shami, Paul J; Smith, B Douglas; Stone, Richard M; Strickland, Stephen A; Wang, Eunice S; Gregory, Kristina M; Naganuma, Maoko

    2013-09-01

    These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that support the recommendations. The updates described in this article focus on the acute promyelocytic leukemia (APL) section, featuring recommendations for additional induction/consolidation regimens in patients with low- or intermediate-risk APL, and providing guidance on maintenance strategies for APL. PMID:24029121

  9. Orbital involvement in chronic lymphocytic leukemia.

    PubMed

    Skinnider, L F; Romanchuk, K G

    1984-04-01

    In a 68-year-old man with chronic lymphocytic leukemia diagnosed on the basis of peripheral lymphocytosis, marked bilateral exophthalmos developed owing to massive orbital involvement by the disease. At the time there was no lymphadenopathy or evidence of organ infiltration. The response to radiotherapy was excellent. Orbital involvement is rare as an early clinical feature of chronic lymphocytic leukemia but should be considered in the differential diagnosis of bilateral exophthalmos in adults. PMID:6733581

  10. Work-related leukemia: a systematic review

    PubMed Central

    2013-01-01

    Leukemia is a complex disease, which only became better understood during the last decades following the development of new laboratory techniques and diagnostic methods. Despite our improved understanding of the physiology of the disease, little is yet known about the causes of leukemia. A variety of potential risk factors have been suggested so far, including personal habits and lifestyle, and a wide range of occupational or environmental exposures. A causal association with leukemia has only been documented to date for ionizing radiation, benzene and treatment with cytostatic drugs, but there is an ongoing scientific debate on the possible association of leukemia with a number of other work-related hazards. In this article, we have reviewed scientific studies, published over the past 5 years, which investigated potential associations between leukemia and exposure to occupational risk factors. The systematic literature review took place via electronic databases, using specific search criteria, and independent reviewers have further filtered the search results to identify the number of articles, presented in our paper. A large number of studies included in the review referred to the effects of ionizing radiation, where new data suggest that the effects of exposure to small doses of ionizing radiation should probably be reevaluated. Some other works appear to substantiate a potential association of the disease with certain pesticides. Further research is also suggested regarding the role of infectious agents or exposure to certain chemicals like formaldehyde or butadiene in the pathogenesis of leukemia. PMID:23697536

  11. Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-03

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-03-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

  13. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-15

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. Cytotoxic efficacy of bendamustine in human leukemia and breast cancer cell lines

    Microsoft Academic Search

    S. Konstantinov; A. Kostovski; M. Topashka-Ancheva; M. Genova; M. Berger

    2002-01-01

    . Purpose: The purpose of this study was to characterise bendamustine's cytotoxic and apoptotic activity in a panel of leukemia and breast cancer cell lines in comparison to its clastogenicity in murine bone marrow. Methods: The cytotoxic effect of bendamustine was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-dye reduction assay. Induction of apoptosis was evidenced by DNA gel electrophoresis, nuclear

  15. Leukemia

    Cancer.gov

    Treatment of Adolescents and Treatment of Adolescents and Young Adults with ALL Young Adults with ALL with an Asparaginase with an Asparaginase - -Intensive Intensive Pediatric Regimen Pediatric Regimen Lewis Silverman, M.D. Lewis Silverman, M.D. Dana

  16. Death resulting from a mesenteric hemorrhage due to acute myeloid leukemia: an autopsy case.

    PubMed

    Suzuki, Hideto; Shigeta, Akio; Fukunaga, Tatsushige

    2014-11-01

    Acute leukemia causes hemorrhage in various sites throughout the body, such as the brain parenchyma, resulting in serious complications. Here, we present an autopsy case where the patient succumbed to a ruptured mesenteric hematoma caused by acute leukemia. A 58-year-old man, without a significant past medical history, was found dead at his workplace. An external examination showed subcutaneous hemorrhage on the left upper extremity. Macroscopic autopsy findings revealed a massive hemoperitoneum (1000mL) and extensive hematoma in the mesentery. Histopathological findings showed monotonous cell proliferation not only in the mesentery, but in many organs, such as the liver, spleen, and kidney; aggregates of the infiltrating cells were also observed in the microvessels of various organs. Immunohistochemical staining indicated that the infiltrating cells showed variable myeloperoxidase positivity, and the cells were strongly positive for CD68 (PG-M1). From the autopsy findings and the immunohistochemical staining, we concluded that the underlying cause of death was acute myeloid leukemia (M5). This case was not only a rare presentation of acute leukemia, but provides a lesson to forensic pathologists regarding noting underlying hematological disease, particularly when a case of massive hemorrhage of unknown etiology is encountered. PMID:25082733

  17. The anticancer potential of flavonoids isolated from the stem bark of Erythrina suberosa through induction of apoptosis and inhibition of STAT signaling pathway in human leukemia HL-60 cells.

    PubMed

    Kumar, Sunil; Pathania, Anup Singh; Saxena, A K; Vishwakarma, R A; Ali, Asif; Bhushan, Shashi

    2013-09-25

    Erythrina suberosa is an ornamental tall tree found in India, Pakistan, Nepal, Bhutan, Burma, Thailand and Vietnam. We have isolated four known distinct metabolites designated as ?-Hydroxyerysotrine, 4'-Methoxy licoflavanone (MLF), Alpinumisoflavone (AIF) and Wighteone. Among the four isolated metabolites the two flavonoids, MLF and AIF were found to be the most potent cytotoxic agent with IC50 of ?20?M in human leukemia HL-60 cells. We are reporting first time the anticancer and apoptotic potential of MLF and AIF in HL-60 cells. Both MLF and AIF inhibited HL-60 cell proliferation and induce apoptosis as measured by several biological endpoints. MLF and AIF induce apoptosis bodies formation, enhanced annexinV-FITC binding of the cells, increased sub-G0 cell fraction, loss of mitochondrial membrane potential (??m), release of cytochrome c, Bax, activation of caspase-9, caspase-3 and PARP (poly ADP Ribose polymers) cleavage in HL-60 cells. MLF and AIF also increase the expression of apical death receptor, Fas, with inhibition of anti-apoptotic protein Bid. All the above parameters revealed that these two flavonoids induce apoptosis through both extrinsic and intrinsic apoptotic pathways in HL-60 cells. In spite of apoptosis, these two flavonoids significantly inhibit nuclear transcription factor NF-?B and STAT (Signal Transducer and Activator of Transcription) signaling pathway, which are highly expressed in leukemia. The present study provide an insight of molecular mechanism of cell death induced by MLF and AIF in HL-60 cells which may be useful in managing and treating leukemia. PMID:23850732

  18. Azacitidine in Treating Patients With Relapsed Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2013-12-10

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  19. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    SciTech Connect

    Wang, Jiying [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)] [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Rao, Qing, E-mail: raoqing@gmail.com [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)] [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)] [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)

    2009-09-04

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  1. PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells

    PubMed Central

    Chang, Fiona T. M.; McGhie, James D.; Chan, F. Lyn; Tang, Michelle C.; Anderson, Melissa A.; Mann, Jeffrey R.; Andy Choo, K. H.; Wong, Lee H.

    2013-01-01

    We have previously shown that ?-thalassemia mental retardation X-linked (ATRX) and histone H3.3 are key regulators of telomeric chromatin in mouse embryonic stem cells. The function of ATRX and H3.3 in the maintenance of telomere chromatin integrity is further demonstrated by recent studies that show the strong association of ATRX/H3.3 mutations with alternative lengthening of telomeres in telomerase-negative human cancer cells. Here, we demonstrate that ATRX and H3.3 co-localize with the telomeric DNA and associated proteins within the promyelocytic leukemia (PML) bodies in mouse ES cells. The assembly of these telomere-associated PML bodies is most prominent at S phase. RNA interference (RNAi)-mediated knockdown of PML expression induces the disassembly of these nuclear bodies and a telomere dysfunction phenotype in mouse ES cells. Loss of function of PML bodies in mouse ES cells also disrupts binding of ATRX/H3.3 and proper establishment of histone methylation pattern at the telomere. Our study demonstrates that PML bodies act as epigenetic regulators by serving as platforms for the assembly of the telomeric chromatin to ensure a faithful inheritance of epigenetic information at the telomere. PMID:23444137

  2. The molecular genetic makeup of acute lymphoblastic leukemia

    Cancer.gov

    Published on Office of Cancer Genomics (https://ocg.cancer.gov) Home > The molecular genetic makeup of acute lymphoblastic leukemia The molecular genetic makeup of acute lymphoblastic leukemia [1] Mullighan CG Hematology Am Soc Hematol Educ Program December

  3. The molecular genetic makeup of acute lymphoblastic leukemia

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > The molecular genetic makeup of acute lymphoblastic leukemia The molecular genetic makeup of acute lymphoblastic leukemia [1] Mullighan CG Hematology Am Soc Hematol Educ Program December

  4. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    MedlinePLUS

    ... lymphocytic leukemia? What are the risk factors for acute lymphocytic leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  5. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePLUS

    ... Topic Additional resources for acute myeloid leukemia What’s new in acute myeloid leukemia research and treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  6. What's New in Adult Acute Lymphocytic Leukemia Research?

    MedlinePLUS

    ... Topic More information about acute lymphocytic leukemia What`s new in acute lymphocytic leukemia research? Researchers at many ... resistance by using other drugs along with chemo. New chemo drugs are also being developed and tested. ...

  7. What's New in Chronic Myeloid Leukemia Research and Treatment?

    MedlinePLUS

    ... Topic Additional resources for chronic myeloid leukemia What`s new in chronic myeloid leukemia research and treatment? Studies ... such as cyclosporine or hydroxychloroquine, with a TKI. New drugs for CML Because researchers now know the ...

  8. What Are the Key Statistics about Chronic Myeloid Leukemia?

    MedlinePLUS

    ... for chronic myeloid leukemia? What are the key statistics about chronic myeloid leukemia? The American Cancer Society's ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  9. What Are the Key Statistics for Chronic Lymphocytic Leukemia?

    MedlinePLUS

    ... for chronic lymphocytic leukemia? What are the key statistics for chronic lymphocytic leukemia? The American Cancer Society's ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

  10. Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

    ClinicalTrials.gov

    2013-02-04

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Meningeal Chronic Myelogenous Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  11. Clinical progression of transplanted large granular lymphocytic leukemia in Fischer 334 rats exposed to 60 Hz magnetic fields

    SciTech Connect

    Morris, James E.(BATTELLE (PACIFIC NW LAB)) [BATTELLE (PACIFIC NW LAB); Sasser, Lyle B.(BATTELLE (PACIFIC NW LAB)) [BATTELLE (PACIFIC NW LAB); Miller, Douglas L.(BATTELLE (PACIFIC NW LAB)) [BATTELLE (PACIFIC NW LAB); Dagle, Gerald E.(WASHINGTON STATE UNIV TC) [WASHINGTON STATE UNIV TC; Rafferty, C N.(Electric Power Research Institute) [Electric Power Research Institute; Ebi, K L.(Electric Power Research Institute) [Electric Power Research Institute; Anderson, Larry E.(BATTELLE (PACIFIC NW LAB)) [BATTELLE (PACIFIC NW LAB)

    1999-01-19

    The purpose of this study was to determine if 60 Hz magnetic fields could alter the clinical progression of leukemia in an animal model. Large granular lymphocytic (LGL) leukemia cells from spleens of leukemic rats were transplanted into young male Fischer rats, producing signs of leukemia in about 2-3 months. The animals were injected with 2.2 x 107 LGL leukemia cells at the initiation of the study and assigned to 4 treatment groups 108/group) as follows: (1) 10 G linearly polarized 60 Hz magnetic fields, (2) sham exposed null energized unit with residual 20 mG fields, (3) ambient controls < 1 mG, and (4) positive controls (a single 5 Gy whole body exposure to 60Co 4 days prior to initiation of exposure). The magnetic fields were activated 20h/day, 7 days/week. Eighteen Rats (18 from each treatment group) were bled, killed, and evaluated at a5, 6, 7, 8, 9, and 11 weeks of exposure. Hematological endpoints, changes in spleen growth, and LGL cell infiltration into the spleen and liver were measured to evaluate the leukemia progression. Significant differences were not detected between the magnetic field exposed groups and the ambient control group, although the clinical progress of leukemia was enhanced in the positive control animals. These data indicate that exposure to sinusoidal, linearly polarized 60 Hz, 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia. Furthermore, the data are in general agreement with previous results of a companion repeated-bleeding study.

  12. Body/bone-marrow differential-temperature sensor

    NASA Technical Reports Server (NTRS)

    Anselmo, V. J.; Berdahl, C. M.

    1978-01-01

    Differential-temperature sensor developed to compare bone-marrow and body temperature in leukemia patients uses single stable amplifier to monitor temperature difference recorded by thermocouples. Errors are reduced by referencing temperatures to each other, not to separate calibration points.

  13. Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-02-07

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  14. Ixazomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-02-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  15. Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-17

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  16. Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-04

    Acute Myeloid Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  17. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-01-29

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  18. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-01-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  19. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2011-11-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  20. AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  1. Daunorubicin Hydrochloride, Cytarabine, and Nilotinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-15

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  4. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 2012-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public Health...Probability of Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more...

  5. Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy

    E-print Network

    Pfeifer, Holger

    Acute Myeloid Leukemia: Nanomedicine drug delivery system could improve chemotherapy Chemotherapy is still the backbone of today's cancer treatment. This is exemplified by acute myeloid leukemia (AML generation anti-leukemia treatments. The results have been published in the Journal of Advanced Healthcare

  6. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...2010-10-01 2010-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public Health...Probability of Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more...

  7. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...2011-10-01 2011-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public Health...Probability of Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more...

  8. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 2013-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public Health...Probability of Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more...

  9. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 2014-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public Health...Probability of Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more...

  10. Leukemia . Author manuscript Controlling TRAIL-mediated caspase-3 activation

    E-print Network

    Paris-Sud XI, Université de

    Leukemia . Author manuscript Page /1 3 Controlling TRAIL-mediated caspase-3 activation Olivier ; Caspases ; metabolism ; Enzyme Activation ; drug effects ; Humans ; Leukemia ; enzymology ; pathology of ( Differential involvement ofLeukemia ` Bax and Bak in TRAIL-mediated apoptosis of leukemic T cells

  11. The allometry of chronic myeloid leukemia Jorge M. Pacheco a

    E-print Network

    Traulsen, Arne

    The allometry of chronic myeloid leukemia Jorge M. Pacheco a , Arne Traulsen b , David Dingli c Available online 10 April 2009 Keywords: Chronic myeloid leukemia Hematopoiesis Modeling Allometry a b s t r a c t Chronic myeloid leukemia (CML) is an acquired neoplastic hematopoietic stem cell (HSC) disorder

  12. Network model of survival signaling in large granular lymphocyte leukemia

    E-print Network

    Albert, Réka

    Network model of survival signaling in large granular lymphocyte leukemia Ranran Zhang , Mithun granular lymphocyte (T-LGL) leukemia features a clonal expansion of antigen-primed, competent, cytotoxic-LGL leukemia, we constructed a T-LGL survival signaling network by integrating the signaling pathways involved

  13. Hairy Cell Leukemia: An Elusive but Treatable Disease

    Microsoft Academic Search

    Sam O. Wanko; Carlos de Castro

    Hairy cell leukemia (HCL) is a unique chronic lympho- proliferative disorder that can mimic or coexist with other clonal hematologic disorders and has been asso- ciated with autoimmune disorders. It should be enter- tained as an alternative diagnosis in patients with cyto- penias being assigned the diagnosis of aplastic anemia, hypoplastic myelodysplastic syndrome, atypical chronic lymphocytic leukemia, B-prolymphocytic leukemia, or

  14. Analysis of fatal intracranial hemorrhage in 792 acute leukemia patients.

    PubMed

    Kim, Hawk; Lee, Je-Hwan; Choi, Seong-Jun; Kim, Woo-Kun; Lee, Jung-Shin; Lee, Kyoo-Hyung

    2004-05-01

    Forty-one of 792 acute leukemia patients suffered fatal intracranial hemorrhage (FICH). Acute promyelocytic leukemia was the most common subtype. Achievement of complete remission in AML was significantly influenced by FICH. FICH accounts for about half of deaths from hemorrhage and this proportion has not changed despite improvements in leukemia management. PMID:15136234

  15. MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Synergistic effect of HMGB1 knockdown and cordycepin in the K562 human chronic myeloid leukemia cell line.

    PubMed

    Chen, Xi; Wang, Ying; Liu, Juan; Xu, Ping; Zhang, Xiao-Min; Tian, Yao-Yao; Xue, Yan-Ming; Gao, Xin-Yu; Liu, Yao; Wang, Jing-Hua

    2015-09-01

    The high-mobility group box 1 (HMGB1) protein is a DNA-binding nuclear protein, which is overexpressed in leukemia cells. Cordycepin is characterized by strong antileukemic properties and is regarded as an effective natural compound for leukemia therapy. The aim of the present study was to investigate the impact of HMGB1 knockdown and cordycepin treatment on proliferation, apoptosis, reactive oxygen species (ROS) levels and adhesion of K562 human chronic myeloid leukemia cells. The Cell Counting kit?8 assay was used to determine the proliferation of K562 cells. The cell cycle and apoptosis of K562 cells was determined using flow cytometric analysis. In addition, a cell adhesion assay was performed. Western blotting was used to determine the protein expression of cyclooxygenase 2, Bax, receptor for advanced glycation end-products and Bcl?2. The data collected demonstrated that HMGB1 knockdown combined with cordycepin treatment had significant anti?proliferative and pro?apoptotic effects. In addition, it increased the ROS levels and reduced the adhesion of K562 cells. It was also identified that HMGB1 knockdown had synergistic effects with cordycepin, which aided in accelerating apoptosis, and inhibiting proliferation and adhesion in chronic myeloid leukemia cells. These results indicated that HMGB1 may be used as a potential therapeutic target, with cordycepin having potential as an auxiliary drug. Therefore, it is suggested that HMGB1 knockdown and corycepin treatement may present a promising therapeutic strategy for leukemia. PMID:26081986

  17. Immunotherapy for Acute Myeloid Leukemia.

    PubMed

    Lichtenegger, Felix S; Krupka, Christina; Köhnke, Thomas; Subklewe, Marion

    2015-07-01

    Despite longstanding efforts in basic research and clinical studies, the prognosis for patients with acute myeloid leukemia (AML) remains poor. About half of the patients are not medically fit for intensive induction therapy to induce a complete remission and are treated with palliative treatment concepts. The patients medically fit for intensive induction therapy have a high complete remission rate but the majority suffers from relapse due to chemo-refractory leukemic cells. Allogeneic stem cell transplantation as post-remission therapy can significantly reduce the likelihood of relapse, but it is associated with a high rate of morbidity and mortality. Novel therapeutic concepts are therefore urgently sought after. During recent years, the focus has shifted towards the development of novel immunotherapeutic strategies. Some of the most promising are drug-conjugated monoclonal antibodies, T-cell engaging antibody constructs, adoptive transfer with chimeric antigen receptor (CAR) T cells, and dendritic cell vaccination. Here, we review recent progress in these four fields and speculate about the optimal time points during the course of AML treatment for their application. PMID:26111468

  18. Obinutuzumab for chronic lymphocytic leukemia.

    PubMed

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

    Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy that is incurable using standard approaches. Two anti-CD20 monoclonal antibodies (mAb), rituximab and ofatumumab, have been approved for CLL treatment. A new glycoengineered type II humanized anti-CD20 mAb, obinutuzumab (GA101), has been developed and demonstrates increased activity against B-cell malignancies by inducing direct cell death and better antibody-dependent cellular cytotoxicity. In a recent randomized Phase III study in patients with newly diagnosed CLL and coexisting conditions, obinutuzumab plus chlorambucil demonstrated significant improvement in progression-free survival and several other outcome parameters, in contrast to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Obinutuzumab represents a promising new option for patients with CLL and must be investigated with other chemotherapy regimens or with new targeted agents. PMID:25163491

  19. Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-06

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  20. Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

    ClinicalTrials.gov

    2015-06-24

    Adult Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Chronic Myelomonocytic Leukemia-1; Chronic Myelomonocytic Leukemia-2; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts

  1. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2015-01-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  2. Acute myeloid leukemia in the pregnant patient.

    PubMed

    Thomas, Xavier

    2015-08-01

    Although acute myeloid leukemia (AML) mostly occurs in older patients, it could be seen in women of childbearing age. It is therefore not surprising that in some patients, the management of AML will be complicated by a coexistent pregnancy. However, the association of leukemia and pregnancy is uncommon. Its incidence is estimated to be 1 in 75 000-100 000 pregnancies. During pregnancy, most leukemias are acute: two-thirds are myeloid and one-third are lymphoblastic. There is no standard approach for this clinical dilemma, in part because of variables such as the type of AML, the seriousness of the symptoms, and the patient's personal beliefs. In many cases, the diagnostic workup has to be altered because of the pregnancy, and often available treatments have varying risks to the fetus. While chemotherapy is reported to have some risks during the first trimester, it is admitted that it can be administered safely during the second and the third trimesters. PMID:25409600

  3. The Pathogenesis of Chronic Lymphocytic Leukemia

    PubMed Central

    Zhang, Suping; Kipps, Thomas J.

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of CD5+CD23+ B cells in blood, marrow, and second lymphoid tissues. Gene-expression profiling and phenotypic studies suggest that CLL is probably derived from CD5+ B cells similar to those found in the blood of healthy adults. Next-generation sequencing has revealed recurrent genetic lesions that are implicated in CLL pathogenesis and/or disease progression. The biology of CLL is entwined with its microenvironment, in which accessory cells can promote leukemia cell growth and/or survival. Recently, much attention has been focused on the CLL B cell receptor (BCR) and on chemokine receptors that enable CLL cells to home to lymphoid tissues and to establish the leukemia microenvironment. Agents that can interfere with BCR signaling or chemokine– receptor signaling, or that target surface antigens selectively expressed on CLL cells, promise to have significant therapeutic benefit in patients with this disease. PMID:23987584

  4. The pathogenesis of chronic lymphocytic leukemia.

    PubMed

    Zhang, Suping; Kipps, Thomas J

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of CD5(+)CD23(+) B cells in blood, marrow, and second lymphoid tissues. Gene-expression profiling and phenotypic studies suggest that CLL is probably derived from CD5(+) B cells similar to those found in the blood of healthy adults. Next-generation sequencing has revealed recurrent genetic lesions that are implicated in CLL pathogenesis and/or disease progression. The biology of CLL is entwined with its microenvironment, in which accessory cells can promote leukemia cell growth and/or survival. Recently, much attention has been focused on the CLL B cell receptor (BCR) and on chemokine receptors that enable CLL cells to home to lymphoid tissues and to establish the leukemia microenvironment. Agents that can interfere with BCR signaling or chemokine-receptor signaling, or that target surface antigens selectively expressed on CLL cells, promise to have significant therapeutic benefit in patients with this disease. PMID:23987584

  5. Adult T-cell leukemia-lymphoma.

    PubMed Central

    Neely, S M

    1989-01-01

    Adult T-cell leukemia-lymphoma, an aggressive T-cell leukemia, is characterized by the presence in the peripheral blood of malignant T cells that have highly indented or lobulated nuclei. Phenotypically the cells are usually helper T cells, but functionally they behave as suppressor cells. Patients have skin and lung involvement, hepatosplenomegaly, moderate lymphadenopathy sparing the mediastinum, and various metabolic abnormalities such as hypercalcemia. The clinical course may be chronic or acute, usually followed by a rapidly progressive terminal course. Adult T-cell leukemia-lymphoma is now known to be caused by human T-cell lymphotropic virus type I, which has been identified in the cells of patients with the disease. PMID:2662614

  6. Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) – a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Patients with acute leukemia experience a substantial symptom burden and are at risk of developing infections throughout the course of repeated cycles of intensive chemotherapy. Physical activity in recent years has been a strategy for rehabilitation in cancer patients to remedy disease and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured and supervised counseling and exercise program. Methods/design This paper presents the study protocol: Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours?+?30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70 - 80%) on an ergometer cycle, strength exercises using hand weights and relaxation exercise. Individual health counseling sessions include a self directed home walk program with a step counter. The primary endpoint is functional performance/exercise capacity (6 minute walk distance). The secondary endpoints are submaximal VO2 max test, sit to stand and bicep curl test, physical activity levels, patient reported outcomes (quality of life, anxiety and depression, symptom prevalence, intensity and interference). Evaluation of clinical outcomes will be explored including incidence of infection, hospitalization days, body mass index, time to recurrence and survival. Qualitative exploration of patients’ health behavior and experiences. Discussion PACE-AL will provide evidence of the effect of exercise and health promotion counseling on functional and physical capacity, the symptom burden and quality of life in patients with acute leukemia during out patient management. The results will inform clinical practice exercise guidelines and rehabilitation programs for patients undergoing treatment for acute leukemia. Optimizing the treatment and care pathway may ease the transition for patients from illness to the resumption of everyday activities. Trial registration ClinicalTrials.gov Identifier: NCT01404520. PMID:24083543

  7. Radiation and the Risk of Chronic Lymphocytic and Other Leukemias among Chornobyl Cleanup Workers

    PubMed Central

    Bazyka, Dimitry; Lubin, Jay H.; Gudzenko, Nataliya; Little, Mark P.; Hatch, Maureen; Finch, Stuart; Dyagil, Irina; Reiss, Robert F.; Chumak, Vadim V.; Bouville, Andre; Drozdovitch, Vladimir; Kryuchkov, Victor P.; Golovanov, Ivan; Bakhanova, Elena; Babkina, Nataliya; Lubarets, Tatiana; Bebeshko, Volodymyr; Romanenko, Anatoly; Mabuchi, Kiyohiko

    2012-01-01

    Background: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear. Objectives: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation. Methods: A nested case–control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986–2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. Results: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = –0.47 (95% CI: < –0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure. Conclusions: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive. PMID:23149165

  8. Adult T-cell leukemia/lymphoma

    PubMed Central

    Burch, Micah; Krause, John R.

    2014-01-01

    Adult T-cell leukemia/lymphoma is a rare malignancy associated with the human retrovirus human T-cell lymphotropic virus type 1. It is characterized by the proliferation of highly pleomorphic lymphocytes. Involvement of peripheral blood, bone marrow, lymph nodes, spleen, and extranodal sites such as skin, liver, gastrointestinal tract, and central nervous system can occur. There are four distinct clinical variants, and the prognosis and clinical course range from highly aggressive to a more protracted course depending on the subtype. We describe a man with de novo adult T-cell leukemia/lymphoma and discuss the unique clinical, morphologic, immunophenotypic, and molecular features of this entity. PMID:24982574

  9. Epidemiology of Childhood Acute Myeloid Leukemia

    PubMed Central

    Puumala, Susan E.; Ross, Julie A.; Aplenc, Richard; Spector, Logan G.

    2013-01-01

    Although leukemia is the most common childhood cancer diagnosis, the subtype, acute myeloid leukemia (AML), is less common and fewer etiologic studies exist. This review summarizes the major risk factors for AML. We searched the literature using PubMed for articles on childhood AML and reviewed 180 articles. While few risk factors are definitive, we identify several with consistent evidence of a possible effect. Thorough analysis of genetic and epigenetic factors is missing from this literature and methodological issues are unresolved. Future studies should more closely examine causal mechanisms, improve exposure measurement, and include analysis using genetic and epigenetic factors. PMID:23303597

  10. Detection of leukemia using electromagnetic waves

    NASA Astrophysics Data System (ADS)

    Colton, David L.; Monk, Peter

    1995-10-01

    The presence of leukemia in bone marrow causes an increase in the electric permittivity and a decrease in the conductivity of the marrow. This suggests the possibility of detecting leukemia by electromagnetic imaging. We show how this can be done for the case of an absorbing host medium (i.e. water) and provide numerical experiments using synthetic data for detecting proliferated tissue at localized portions of the bone marrow. We do not assume that the refractive index of the fat, bone, and muscle are known but will instead recover these values as part of the imaging process.

  11. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    ClinicalTrials.gov

    2014-11-12

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  12. Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-10

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  13. Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-02

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  14. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-04-24

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  15. Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-04

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-05

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  17. Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  18. How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet

    PubMed Central

    Béné, Marie C.; Kaeda, Jaspal S.

    2009-01-01

    Resistance to therapeutic agents is a major factor in the failure of cancer treatments. In leukemia, the resistant cells remaining in the bone marrow and/or peripheral blood constitute minimal residual disease and are detectable by highly sensitive assays when the patient appears to be in complete remission. Early detection of the expansion of residual cells permits clinical intervention with the aim of reversing the proliferation of resistant leukemic cells. Therefore, accurate and precise measurement of minimal residual disease can greatly enhance optimization of oncology patients' clinical management. This notion is supported by a large body of data among chronic myeloid leukemia patients, but minimal residual disease detection and monitoring is increasingly applied to other types of leukemia, and is starting to be a factor in decision-making for some therapeutic trials in childhood acute lymphoblastic leukemia. Here, from the solid ground of minimal residual disease detection in chronic myeloid leukemia, the current state of the art and development of molecular techniques in other leukemias and the growing field of multiparameter flow cytometry are reviewed in two separate parts reporting on the respective advances, advantages and pitfalls of these emerging methods. PMID:19586938

  19. Characterization of Nuclear Localization and SUMOylation of the ATBF1 Transcription Factor in Epithelial Cells

    PubMed Central

    Sun, Xiaodong; Li, Jie; Dong, Frederick N.; Dong, Jin-Tang

    2014-01-01

    ATBF1/ZFHX3 is a large transcription factor that functions in development, tumorigenesis and other biological processes. ATBF1 is normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells. The mechanism underlying the mislocalization of ATBF1 is unknown. In this study, we analyzed the nuclear localization of ATBF1, and found that ectopically expressed ATBF1 formed nuclear body (NB)-like dots in the nucleus, some of which indeed physically associated with promyelocytic leukemia (PML) NBs. We also defined a 3-amino acid motif, KRK2615-2617, as the nuclear localization signal (NLS) for ATBF1. Interestingly, diffusely distributed nuclear SUMO1 proteins were sequestered into ATBF1 dots, which could be related to ATBF1's physical association with PML NBs, known SUMOylation hotspots. Furthermore, ATBF1 itself was SUMOylated. ATBF1 SUMOylation occurred at more than 3 lysine residues including K2349, K2806 and K3258 and was nuclear specific. Finally, the PIAS3 SUMO1 E3 ligase, which interacts with ATBF1 directly, diminished rather than enhanced ATBF1 SUMOylation, preventing the co-localization of ATBF1 with SUMO1 in the nucleus. These findings suggest that nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes. PMID:24651376

  20. Newly Diagnosed Acute Promyelocytic Leukemia

    PubMed Central

    Avvisati, Giuseppe

    2011-01-01

    Acute promyelocytic leukemia (APL) represents a medical emergency with a high rate of early mortality. As a consequence, as soon as the diagnosis is suspected based upon cytologic criteria, it is necessary to start all- trans retinoic acid (ATRA) treatment without delay. For patients with newly diagnosed APL, induction therapy with ATRA plus anthracycline based chemotherapy is recommended. At present the combination of arsenic trioxide plus ATRA should be considered for patients who are not candidates for anthracycline-based therapy. For pediatric and adult patients with APL aged < 60 years who achieve a CR with induction, I recommend 3 intensive courses of consolidation chemotherapy associated to ATRA, targeted on the basis of the risk group at diagnosis. In patients treated with a very intensive consolidation chemotherapy maintenance treatment can be omitted. However If a maintenance treatment has to be adopted I suggest the use of intermittent ATRA for 15 days every 3 months for a period of 2 years, rather than ATRA associated to chemotherapy. Moreover, taking into account the medical literature, a reduced dosage of ATRA ( 25 mg/m2) in pediatric patients and a consolidation chemotherapy of reduced intensity in elderly patients is recommended. Furthermore, in order to maximize survival, careful attention should be reserved to the coagulopathy and to the appearance of the differentiation syndrome. Finally, PCR for the PML/RARA fusion gene on a bone marrow specimen every three months for two years, and then every six months for additional three years are needed during the follow-up. PMID:22220261

  1. Management of chronic lymphocytic leukemia.

    PubMed

    Stilgenbauer, Stephan; Furman, Richard R; Zent, Clive S

    2015-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for "active disease," which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care. PMID:25993154

  2. Morphological diagnoses of the Japan adult leukemia study group acute myeloid leukemia protocols: central review.

    PubMed

    Kuriyama, K; Tomonaga, M; Kobayashi, T; Takeuchi, J; Ohshima, T; Furusawa, S; Saitoh, K; Ohno, R

    2001-01-01

    A morphological review system of the Japan Adult Leukemia Study Group has developed from the AML-87 through the AML-92 experience. We reviewed 1427 (90%) of 1592 cases enrolled in the AML-87, -89, or -92 protocols for morphology; 1408 (88%) were eligible. The rate of diagnostic concordance between each institute and the Committee on Morphological Diagnosis ranged from 76% to 80%. Acute myeloid leukemia (AML) subtypes were as follows: AML M0, 27 (2%); M1, 179 (13%); M2, 472 (34%); M3, 358 (25%); M4, 265 (19%); M5, 57 (4%); M6, 39 (3%); and M7, 11 (1%). The reason for the high number of patients with AML M3 is that many M3 patients were enrolled in the AML-92 protocol, which contained all-trans-retinoic acid. AML M0, M6 and M7 belonged to the poor prognostic groups. Auer bodies were found in 284 (53%) of 538 patients who survived significantly longer than those without Auer bodies in AML-87/-89. In AML-92 except for AML M3, 259 (43%) of 602 cases were Auer+ and also showed better survival rates. The survival of patients with >50% myeloperoxidase (MPO)-positive blast cells was better than those with < or =50% MPO+ blast cells in AML-87/-89. This trend was also seen in AML-92 excluding M3. AML with trilineage dysplasia (AML/TLD) is characterized as a subtype of de novo AML that shows morphological dysplasia of mature hematopoietic cells on a background of leukemic blast cells The number of patients with AML/TLD was 89 (16.5%) of 545 patients reviewed in AML-87/-89. AML-92, except for M3, showed a higher rate of patients with TLD (161 cases; 27.6%) because there were no patients with TLD in the AML M3 group. Survival rates for AML/TLD were worse than those for AML/non-TLD in both the AML-87/-89 and -92 protocols. Eighty percent of all cases (793/986) entered in AML-92 were analyzed cytogenetically. Fifty-one cases were not available for karyotyping because of a lack of mitoses or inappropriate preparations. The most frequent karyotype was normal, which accounted for 34.2%. The t(15;17), t(8;21), and inv(16) karyotypes, which are regarded as good risk factors, were 23.8%, 9.2%, and 1.6%, respectively. Abnormal chromosomes 5, 7, t(9;22), and t(6;9) were considered to be poor or intermediate risk factors As a new system of karyotyping begins in the ongoing AML protocol, useful chromosomal data will be obtained in the near future. PMID:11372762

  3. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2015-01-08

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Cognitive/Functional Effects; Neurotoxicity; Pain; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Therapy-related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  5. Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

    Microsoft Academic Search

    Shabnam Shalapour; Cornelia Eckert; Karl Seeger; Madlen Pfau; Javier Prada; Günter Henze; Thomas Blankenstein; Thomas Kammertoens

    2010-01-01

    Childhood acute lymphoblastic leukemia (ALL) is caused by malignant immature lymphocytes. Even though childhood ALL can be\\u000a cured in a large number of patients, around 20% of the patients suffer a relapse after chemotherapy. The origin of the relapse\\u000a is unclear at the present time. Given the high plasticity of cells, we searched for leukemia-associated genetic aberrations\\u000a and immunoglobulin (IG)

  6. Estimation of internal exposure of the thyroid to (131)I on the basis of (134)Cs accumulated in the body among evacuees of the Fukushima Daiichi Nuclear Power Station accident.

    PubMed

    Hosoda, Masahiro; Tokonami, Shinji; Akiba, Suminori; Kurihara, Osamu; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Momose, Takumaro; Nakano, Takashi; Mariya, Yasushi; Kashiwakura, Ikuo

    2013-11-01

    Namie Town was heavily contaminated by the Fukushima Daiichi Nuclear Power Station accident. The thyroid equivalent dose for residents who lived in Namie was estimated using results of whole body counting examinations which were carried out by the Japan Atomic Energy Agency a few months after the nuclear accident. Photon peaks of (131)I and (134)Cs were previously measured by the authors using a NaI(Tl) scintillation spectrometer and that information was used to estimate the (131)I/(134)Cs activity ratio of total intake in the present study. The maximum values of (131)I/(134)Cs activity ratio corresponding to thyroid uptake factors of 0.3, 0.1 and 0.03 were evaluated to be 0.9, 2.6 and 8.7, respectively. The maximum value of the (131)I/(134)Cs activity ratio was used to obtain the most conservative thyroid equivalent dose estimation. The maximum internal exposure of the thyroid to (131)I on the basis of (134)Cs accumulated in the body measured by the whole body counter was estimated to be 18mSv. This value was much smaller than 50mSv that the International Atomic Energy Agency recommends as the dose at which exposed persons should take stable iodine tablets. PMID:24103348

  7. Therapeutic Autologous Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2011-07-12

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  8. Neuropsychological Functioning in Survivors of Childhood Leukemia.

    ERIC Educational Resources Information Center

    Reeb, Roger N.; Regan, Judith M.

    1998-01-01

    Examined neuropsychological functioning of survivors of acute lymphoblastic leukemia who underwent central-nervous-system prophylactic treatment. Findings replicated past research in showing survivors perform poorly on visual-motor integration tasks and develop a Nonverbal Learning Disability. Findings offer recommendations for future research and…

  9. Psychotherapy for Some Anxiety Sequelae of Leukemia.

    ERIC Educational Resources Information Center

    Stokes, Trevor

    1999-01-01

    This case study describes use of a program of self-mediated recording and intervention, including distraction techniques, with monitoring within the family, with an 8-year-old child with leukemia and a generalized anxiety about health. Anxiety was reduced to the normal range and maintained at that level at a nine-month followup assessment.…

  10. Dental Treatment in Patients with Leukemia

    PubMed Central

    Meurer, Maria Inês; Grando, Liliane Janete; Gonzaga Del Moral, Joanita Ângela; da Silva Rath, Inês Beatriz; Schaefer Tavares, Silvia

    2015-01-01

    Dental treatment of patients with leukemia should be planned on the basis of antineoplastic therapy which can be chemotherapy with or without radiotherapy and bone marrow transplantation. Many are the oral manifestations presented by these patients, arising from leukemia and/or treatment. In addition, performing dental procedures at different stages of treatment (before, during, or after) must follow certain protocols in relation to the haematological indices of patients, aimed at maintaining health and contributing to the effectiveness of the results of antineoplastic therapy. Through a literature review, the purpose of this study was to report the hematological abnormalities present in patients with leukemia, trying to correlate them with the feasibility of dental treatment at different stages of the disease. It is concluded in this paper that dental treatment in relation to haematological indices presented by patients with leukemia must follow certain protocols, mainly related to neutrophil and platelet counts, and the presence of the dentist in a multidisciplinary team is required for the health care of this patient. PMID:25784937

  11. Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

    PubMed Central

    Kawasaki, Yukako; Makimoto, Masami; Nomura, Keiko; Hoshino, Akihiro; Hamashima, Takeru; Hiwatari, Mitsuteru; Nakazawa, Atsuko; Takita, Junko; Yoshida, Taketoshi; Kanegane, Hirokazu

    2015-01-01

    Key Clinical Message We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15-MKL1 fusion gene. PMID:25838902

  12. Leukemia in Hiroshima City Atomic Bomb Survivors

    Microsoft Academic Search

    Niel Wald

    1958-01-01

    An attempt is made to establish a quantitative relation between ; radiation-induced leukemia and the unit-dose of radiation received. Data are ; presented which are based on studies of the survivors of the atomic bombings in ; Hiroshima City, Japan. (C.H.);

  13. Genomic Approaches to Chronic Lymphocytic Leukemia

    PubMed Central

    Improgo, Ma. Reina; Brown, Jennifer R.

    2013-01-01

    Synopsis This article discusses recent advances in genomic approaches used to understand chronic lymphocytic leukemia (CLL). We describe tools for analyzing DNA sequence level alterations, summarize data obtained from these various platforms, and discuss the clinical relevance of these findings. PMID:23561468

  14. Paranasal Sinus Involvement in Acute Lymphoblastic Leukemia

    Microsoft Academic Search

    Bo-Hung Chang; Ying-Lin Chen; Ta-Jen Lee; Li-Ang Lee; Shuen-Kuei Liao

    Acute lymphoblastic leukemia (ALL) is a hemopoietic malignancy of the bone marrow that rarely invades the sinonasal area. If infiltration of paranasal sinuses occurs, it may lead to rhinosinusitis and orbital complications that need aggressive treatment. In this report, a 26-year-old male patient who had a history of ALL and had one relapse, suffered from rapid progression of right periorbital

  15. Expectancy for Life in Chronic Lymphatic Leukemia

    Microsoft Academic Search

    ROBERT A. GREEN; HUBERT DIXON

    1965-01-01

    leukemia, and it is not clear what the real prospects for survival are in this group of diseases. We have impressions of a variable chronicity, but there is need for standards if the results of new methods of treatment are to be meaningful, and it is important to know how valid the standard series are. Obvious reasons, in terms of

  16. General Information about Adult Acute Myeloid Leukemia

    MedlinePLUS

    ... is available from the NCI Web site . To Learn More About Adult Acute Myeloid Leukemia Cancer For more information from ... regularly and updated as needed, by the PDQ Adult Treatment Editorial ... what has been learned in the laboratory. Each trial answers certain scientific ...

  17. Stages of Adult Acute Myeloid Leukemia

    MedlinePLUS

    ... is available from the NCI Web site . To Learn More About Adult Acute Myeloid Leukemia Cancer For more information from ... regularly and updated as needed, by the PDQ Adult Treatment Editorial ... what has been learned in the laboratory. Each trial answers certain scientific ...

  18. Leukemia immune changes following massage therapy

    Microsoft Academic Search

    Tiffany Field; Christy Cullen; Miguel Diego; Maria Hernandez-Reif; Phillippa Sprinz; Kristen Beebe; Bonnie Kissell; Vivian Bango-Sanchez

    2001-01-01

    Twenty children with leukemia were provided with daily massage therapy by their parents and were compared to a standard treatment control group. Following a month of massage therapy, depressed mood decreased in the children's parents, and the children's white blood cell and neutrophil counts increased.

  19. Arsenic trioxide (As?O?) inhibits murine WEHI-3 leukemia in BALB/c mice in vivo.

    PubMed

    Lai, Tung-Yuan; Lin, Jen-Jyh; Huang, Wen-Wen; Kuo, Shu-Chu; Wen, Yen-Fang; Lai, I-Cheng; Lin, Chin-Chung; Yang, Jai-Sing; Chung, Jing-Gung

    2012-05-01

    Arsenic trioxide (As?O?) is used clinically to treat acute promyelocytic leukemia (APL) and has activity in vitro for induction of apoptosis in several solid tumor cell lines. To investigate the potential therapeutic application of As?O? for leukemia, we analyzed the effects of As?O? on the WEHI-3 cells-induced orthotopic leukemia animal model in vivo in this study. We established the WEHI-3 cells leukemia mice through the injection of murine WEHI-3 cells into BALB/c mice, and they were then treated with As?O? (0.9 and 4.5 mg kg?¹ ; p.o.) and/or combined with all-trans-retinoic acid (ATRA), (30 mg kg?¹ ; i.p.). The results indicated that (1) As?O? alone or As?O? combined with ATRA promoted the total survival rate of leukemia mice and these effects are dose-dependent; (2) As?O? did not affect the body weight but decreased the spleen weight; however, it did not affect liver weight; (3) As?O? alone or As?O? combined with ATRA increased the levels of CD3 and CD19, indicating that the differentiation of T and B cells were promoted; and (4) As?O? alone or As?O? combined with ATRA did not change the levels of Mac-3 and CD11b markers, indicating that the differentiation of the precursor of macrophage were not inhibited. Based on these observations, As?O? alone or As?O? combined with ATRA have efficacious antileukemia activity in WEHI-3 cells leukemia in vivo. PMID:20886602

  20. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    ClinicalTrials.gov

    2015-05-27

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  1. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  2. Investigating Childhood Leukemia in Churchill County, Nevada

    PubMed Central

    Rubin, Carol S.; Holmes, Adrianne K.; Belson, Martin G.; Jones, Robert L.; Flanders, W. Dana; Kieszak, Stephanie M.; Osterloh, John; Luber, George E.; Blount, Benjamin C.; Barr, Dana B.; Steinberg, Karen K.; Satten, Glen A.; McGeehin, Michael A.; Todd, Randall L.

    2007-01-01

    Background Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected. Objectives In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case-comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families. Methods Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals. Results The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values; however, levels were similar among case and comparison groups. Conclusions Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters. PMID:17366836

  3. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-12

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  4. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia

    E-print Network

    Takahashi, Ryo

    leukemia Highlights Wholeexome sequencing analysis identified that SETBP1 and JAK3 genes were among common targets for secondary mutations in juvenile myelomonocytic leukemia (JMML), an intractable pediatric leukemia with poor prognosis. These newly identified gene mutations were often subclonal

  6. 28 CFR 79.12 - Criteria for eligibility for claims relating to leukemia.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...for eligibility for claims relating to leukemia. 79.12 Section 79.12 Judicial...Eligibility Criteria for Claims Relating to Leukemia § 79.12 Criteria for eligibility for claims relating to leukemia. To establish eligibility...

  7. TRANSLATION OF BOVINE LEUKEMIA VIRUS GENOME INFORMATION IN HETEROLOGOUS PROTEIN SYNTHESIZING SYSTEMS

    E-print Network

    Paris-Sud XI, Université de

    TRANSLATION OF BOVINE LEUKEMIA VIRUS GENOME INFORMATION IN HETEROLOGOUS PROTEIN SYNTHESIZING, probablement situé du côté 3' du génome viral. Introduction. Bovine leukemia is a lymphoproliferative disease whose etiological agent is a retrovirus called Bovine Leukemia Virus (BLV). The cha- racteristics

  8. 28 CFR 79.12 - Criteria for eligibility for claims relating to leukemia.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...for eligibility for claims relating to leukemia. 79.12 Section 79.12 Judicial...Eligibility Criteria for Claims Relating to Leukemia § 79.12 Criteria for eligibility for claims relating to leukemia. To establish eligibility...

  9. 28 CFR 79.12 - Criteria for eligibility for claims relating to leukemia.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...for eligibility for claims relating to leukemia. 79.12 Section 79.12 Judicial...Eligibility Criteria for Claims Relating to Leukemia § 79.12 Criteria for eligibility for claims relating to leukemia. To establish eligibility...

  10. 28 CFR 79.12 - Criteria for eligibility for claims relating to leukemia.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...for eligibility for claims relating to leukemia. 79.12 Section 79.12 Judicial...Eligibility Criteria for Claims Relating to Leukemia § 79.12 Criteria for eligibility for claims relating to leukemia. To establish eligibility...

  11. 28 CFR 79.12 - Criteria for eligibility for claims relating to leukemia.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...for eligibility for claims relating to leukemia. 79.12 Section 79.12 Judicial...Eligibility Criteria for Claims Relating to Leukemia § 79.12 Criteria for eligibility for claims relating to leukemia. To establish eligibility...

  12. What If the Leukemia Doesn't Respond or Comes Back After Treatment? (ALL)

    MedlinePLUS

    ... Local ACS Learn About Cancer » Leukemia - Acute Lymphocytic (ALL) in Adults » Detailed Guide » What if the leukemia ... Download Printable Version [PDF] » Treating Leukemia - Acute Lymphocytic (ALL) in Adults TOPICS Document Topics GO » SEE A ...

  13. Genome wide analysis of acute myeloid leukemia reveal leukemia specific methylome and subtype specific hypomethylation of repeats.

    PubMed

    Saied, Marwa H; Marzec, Jacek; Khalid, Sabah; Smith, Paul; Down, Thomas A; Rakyan, Vardhman K; Molloy, Gael; Raghavan, Manoj; Debernardi, Silvana; Young, Bryan D

    2012-01-01

    Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R(2) = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array. PMID:22479372

  14. Genome Wide Analysis of Acute Myeloid Leukemia Reveal Leukemia Specific Methylome and Subtype Specific Hypomethylation of Repeats

    PubMed Central

    Saied, Marwa H.; Marzec, Jacek; Khalid, Sabah; Smith, Paul; Down, Thomas A.; Rakyan, Vardhman K.; Molloy, Gael; Raghavan, Manoj; Debernardi, Silvana; Young, Bryan D.

    2012-01-01

    Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R2?=?0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array. PMID:22479372

  15. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2015-05-18

    Chronic Lymphocytic Leukemia in Remission; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma

  16. Exposure to ambient air pollution in Canada and the risk of adult leukemia.

    PubMed

    Winters, Nicholas; Goldberg, Mark S; Hystad, Perry; Villeneuve, Paul J; Johnson, Kenneth C

    2015-09-01

    There is a paucity of studies investigating adult leukemia and air pollution. To address this gap, we analyzed data from a Canadian population-based case-control study conducted in 1994-1997. Cases were 1064 adults with incident leukemia and controls were 5039 healthy adults. We used data from satellites and fixed-site monitoring stations to estimate residential concentrations of NO2 and fine particulate matter (PM2.5) for the period prior to diagnosis, starting in 1975 and ending in 1994. We modeled the average annual exposure of each subject. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated using logistic regression, adjusted for age, gender, province, smoking, education, body mass index, income, and self-reported exposures to ionizing radiation and benzene. We found an 'n-shaped' response function between exposure to NO2 and all forms of leukemia: from the tenth percentile to the median (4.51 to 14.66ppb), the OR was 1.20; 95% CI: 0.97-1.48 and from the 75th percentile to the 90th (22.75 to 29.7ppb), the OR was 0.79; 95% CI 0.68-0.93. For PM2.5 we found a response function consistent with a linear model, with an OR per 10?g/m(3) of 0.97 (95% CI 0.75-1.26). For chronic lymphocytic leukemia we found response functions that were consistent with a simple linear model, with an OR per 5ppb of NO2 of 0.93 (95% CI 0.86-1.00) and an OR per 10?g/m(3) of PM2.5 of 0.62 (95% CI 0.42-0.93). In summary, for chronic lymphocytic leukemia we found no evidence of an association with air pollution and with all forms of leukemia we found weak evidence of an association only at low concentrations of NO2. It is possible that these inconsistent results may have arisen because of unaccounted urban/rural differences or possibly from a selection effect, especially among controls. PMID:25955692

  17. Laboratory diagnosis of chronic myelomonocytic leukemia and progression to acute leukemia in association with chronic lymphocytic leukemia: morphological features and immunophenotypic profile.

    PubMed

    Santos, Iris Mattos; Franzon, Carine Muniz Ribeiro; Koga, Adolfo Haruo

    2012-01-01

    Chronic myelomonocytic leukemia is a clonal stem cell disorder that is characterized mainly by absolute peripheral monocytosis. This disease can present myeloproliferative and myelodysplastic characteristics. According to the classification established by the World Health Organization, chronic myelomonocytic leukemia is inserted in a group of myeloproliferative/myelodysplastic disorders; its diagnosis requires the presence of persistent monocytosis and dysplasia involving one or more myeloid cell lineages. Furthermore, there should be an absence of the Philadelphia chromosome and the BCR/ABL fusion gene and less than 20% blasts in the blood or bone marrow. Phenotypically, the cells in chronic myelomonocytic leukemia can present myelomonocytic antigens, such as CD33 and CD13, overexpressions of CD56 and CD2 and variable expressions of HLA-DR, CD36, CD14, CD15, CD68 and CD64. The increase in the CD34 expression may be associated with a transformation into acute leukemia. Cytogenetic alterations are frequent in chronic myelomonocytic leukemia, and molecular mutations such as NRAS have been identified. The present article reports on a case of chronic myelomonocytic leukemia, diagnosed by morphologic and phenotypical findings that, despite having been suggestive of acute monocytic leukemia, were differentiated through a detailed analysis of cell morphology. Furthermore, typical cells of chronic lymphocytic leukemia were found, making this a rare finding. PMID:23049428

  18. [Markers of metabolic syndrome and peptides regulating metabolism in survivors of childhood acute lymphoblastic leukemia].

    PubMed

    Skocze?, Szymon; Tomasik, Przemys?aw; Balwierz, Walentyna; Surmiak, Marcin; Sztefko, Krystyna; Galicka-Lata?a, Danuta

    2011-01-01

    Along with the growing epidemic of overweight the risk of atherosclerosis, cardiovascular disease morbidity and mortality are increasing markedly. Metabolic syndrome (MS) is a condition clustering together several risk factors of those complications such as visceral obesity, glucose intolerance, arterial hypertension and dislipidemia. The risk of obesity in acute lymphoblastic leukemia (ALL) survivors is higher than in general population. We aimed to assess (1) the relationships between chosen adipokines and neuropeptides, chemotherapy, CRT, and body fatness and (2) evaluate adipokines and neuropeptides concentrations as a new markers of MS in children. We conducted cross-sectional evaluation of 82 ALL survivors (median age: 13.2 years; range: 4,8-26,2; median time from treatment: 3.2 years), including fasting laboratory testing: peptides (leptin, GLP-1, orexin, PYY, apelin), total cholesterol and its fractions, triglycerides; anthropometric measurements (weight, height), systolic and diastolic blood pressure. We estimated percentiles of body mass index and percentiles of blood pressure. Between 82 survivors overweight and diastolic hypertension was diagnosed in 31% of patients (35% in CRT group) and 15% respectively. At least one abnormality in lipids concentrations was found in 43%. Girls were more affected than boys. Statistically significant increased in leptin and apelin concentrations and decreased in soluble leptin receptor concentrations in the overweight group were observed compared to the non overweight subjects. Significant increase in orexin levels in females who had received CRT compared to those who had not received CRT was found. CRT is the main risk factor of elevated of body mass among survivors of childhood leukemia. Dyslipidemia and hypertension, along with increased adiposity indicate higher risk of MS development. Girls are more affected than boys. Leptin, orexin and apelin seem to be good markers of increased adiposity especially after CRT. Higher leptin levels may be related to central resistance to those peptides. Survivors of childhood acute lymphoblastic leukemia should be screened for markers of the metabolic syndrome. PMID:22335007

  19. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  20. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-10

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  2. Body Piercing

    PubMed Central

    Koenig, Laura M; Carnes, Molly

    1999-01-01

    OBJECTIVE To review the current information on medical complications, psychological implications, and legislative issues related to body piercing, a largely unregulated industry in the United States. METHODS We conducted a MEDLINE search of English language articles from 1966 until May 1998 using the search terms “body piercing” and “ear piercing.” Bibliographies of these references were reviewed for additional citations. We also conducted an Internet search for “body piercing” on the World Wide Web. MAIN RESULTS: In this manuscript, we review the available body piercing literature. We conclude that body piercing is an increasingly common practice in the United States, that this practice carries substantial risk of morbidity, and that most body piercing in the United States is being performed by unlicensed, unregulated individuals. Primary care physicians are seeing growing numbers of patients with body pierces. Practitioners must be able to recognize, treat, and counsel patients on body piercing complications and be alert to associated psychological conditions in patients who undergo body piercing. PMID:10354260

  3. Dasatinib in Imatinib-Resistant Philadelphia Chromosome–Positive Leukemias

    Microsoft Academic Search

    Moshe Talpaz; Neil P. Shah; Hagop Kantarjian; Nicholas Donato; John Nicoll; Ron Paquette; Jorge Cortes; Susan O'Brien; Claude Nicaise; Eric Bleickardt; M. Anne Blackwood-Chirchir; Vishwanath Iyer; Tai-Tsang Chen; Fei Huang; Arthur P. Decillis; Charles L. Sawyers

    2006-01-01

    Background The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromo- some-positive (Ph-positive) leukemias, but relapse occurs, mainly as a result of the outgrowth of leukemic subclones with imatinib-resistant BCR-ABL mutations. We evaluated dasatinib, a BCR-ABL inhibitor that targets most imatinib-resistant BCR- ABL mutations, in patients with chronic myelogenous leukemia (CML) or Ph-positive acute lymphoblastic leukemia (ALL). Methods Patients

  4. Human Promyelocytic Leukemia Cells in Culture Differentiate into Macrophage-Like Cells when Treated with a Phorbol Diester

    Microsoft Academic Search

    Giovanni Rovera; Daniela Santoli; Caroline Damsky

    1979-01-01

    When suspension cultures of human promyelocytic leukemia cells (line HL60) were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA; 1.6-160 nM), more than 80% of the cells adhered to the plastic substrate within 24 hr. Within the same time period the immature azurophilic granulations typical of HL60 promyelocytic cells disappeared and the nuclear chromatin became more condensed, but the nucleolus was retained. The

  5. Common acute lymphoblastic leukemia antigen expressed on leukemia and melanoma cell lines has neutral endopeptidase activity.

    PubMed Central

    Jongeneel, C V; Quackenbush, E J; Ronco, P; Verroust, P; Carrel, S; Letarte, M

    1989-01-01

    We have previously reported that the amino acid sequence of the common acute lymphoblastic leukemia antigen (CALLA, CD10) translated from a normal human kidney cDNA clone is identical to that of neutral endopeptidase (NEP, EC 3.4.24.11). In this study, we show that by flow cytometry, a monoclonal antibody (135A3) produced against rabbit NEP reacted selectively with leukemia and melanoma cell lines expressing CALLA on their surface. A glycoprotein of apparent Mr 100,000 was immunoprecipitated from surface labeled NALM-1 leukemia or Mel-1477 melanoma cells with monoclonal antibodies to NEP (135A3) or CALLA (44C10). mRNAs hybridizing to a NEP-specific probe were present in CALLA+ leukemia and melanoma cell lines, but absent from CALLA- lines. NEP enzymatic activity was detected on intact cells from CALLA+ lines, but not CALLA- lines. The activity was blocked by two selective inhibitors of NEP, thiorphan and phosphoramidon. CALLA antigen purified from the NALM-6 leukemic cell line by affinity to 44C10-IgG Sepharose retained a peptidase activity that was completely blocked by thiorphan and phosphoramidon. Thus the CALLA antigen present at the surface of leukemia and melanoma cell lines is an enzymatically active neutral endopeptidase. Images PMID:2521492

  6. Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).

    PubMed

    Crespo-Solis, Erick; López-Karpovitch, Xavier; Higuera, Jesús; Vega-Ramos, Beatriz

    2012-10-01

    Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious complication in patients with acute leukemia. One of the major problems of this complication is the diagnosis process itself. CSF cytology is currently considered the gold standard for establishing the diagnosis, a technique which presents various processing limitations, seriously impacting the predictive values. In the last 11 years, studies of CSF flow cytometry analysis done in patients with acute leukemia have demonstrated superiority in comparison with CSF cytology. Although comparative studies between these two techniques have been reported since 2001, no new consensus or formal changes to the gold standard have been established for the CSF acute leukemia diagnosis. The evidence suggests that positive flow cytometry cases, considered as indeterminate cases, will behave like disease in the central nervous system (CNS). Nevertheless, we think there are some variables and considerations that must be first evaluated under research protocols before CNS relapse can be established with only one positive flow cytometry analysis in the setting of indeterminate CSF samples. This paper proposes a diagnostic algorithm and complementary strategies. PMID:22639108

  7. Graffi murine leukemia virus: molecular cloning and characterization of the myeloid leukemia-inducing agent.

    PubMed Central

    Ru, M; Shustik, C; Rassart, E

    1993-01-01

    The Graffi murine leukemia virus (MuLV) is a retroviral mixture that induces predominantly myeloid leukemia in several inbred strains of mice. To analyze the viral component responsible for the myeloid leukemogenesis, we cloned several proviruses from a Graffi MuLV-infected cell line. Several infectious molecular clones were obtained that could be classified into two distinct groups of infectious MuLV. Both types of MuLV were nondefective, ecotropic, and NB tropic and induced granulocytic leukemia in BALB/c and NFS mice. Restriction enzyme analysis and molecular hybridization with several MuLV probes on one molecular clone from each group revealed that both groups are closely related to each other but are clearly distinct from all known retroviruses. One component of MuLV, however, induced leukemia with a shorter latency period and harbored a lengthier long terminal repeat. The long terminal repeat of the more leukemogenic component of MuLV had acquired a 60-bp perfect duplication in the U3 region. Analysis of the tumor DNAs with probes for the mouse T-cell receptor and immunoglobulin heavy chain genes revealed frequent rearrangements with one or both probes. This concomitant expression by leukemic cells of markers of different lineages, observed in human leukemias, has been termed "lineage infidelity" and confirms that the latter rearrangements are not restricted to hematopoietic precursors committed to lymphoid differentiation. Images PMID:8392610

  8. The Biology and Targeting of FLT3 in Pediatric Leukemia

    PubMed Central

    Annesley, Colleen E.; Brown, Patrick

    2014-01-01

    Despite remarkable improvement in treatment outcomes in pediatric leukemia over the past several decades, the prognosis for high-risk groups of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), as well as for relapsed leukemia, remains poor. Intensification of chemotherapy regimens for those at highest risk has improved success rates, but at the cost of significantly increased morbidity and long-term adverse effects. With the success of imatinib in Philadelphia-chromosome-positive leukemia and all-trans retinoic acid in acute promyelocytic leukemia, the quest to find additional molecularly targeted therapies has generated much excitement over recent years. Another such possible target in pediatric acute leukemia is FMS-like tyrosine kinase 3 (FLT3). FLT3 aberrations are among the most frequently identified transforming events in AML, and have significant clinical implications in both high-risk pediatric AML and in certain high-risk groups of pediatric ALL. Therefore, the successful targeting of FLT3 has tremendous potential to improve outcomes in these subsets of patients. This article will give an overview of the molecular function and signaling of the FLT3 receptor, as well as its pathogenic role in leukemia. We review the discovery of targeting FLT3, discuss currently available FLT3 inhibitors in pediatric leukemia and results of clinical trials to date, and finally, consider the future promise and challenges of FLT3 inhibitor therapy. PMID:25295230

  9. Cytogenetic and molecular studies of down syndrome individual with leukemia

    SciTech Connect

    Shen, J.J.; Hassold, T.J. [Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States); Williams, B.J. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States); Zupursky, A.; Doyle, J. [Univ. of Toronto (Canada); Sherman, S.L. [Emory Univ. School of Medicine, Atlanta, GA (United States); Jacobs, P.A. [Salisbury District Hospital (United Kingdom); Shugar, A.L.; Soukup, S.W. [Univ. of Cincinnati, OH (United States)

    1995-04-01

    There is an increased risk of leukemia in Down syndrome (DS) patients, with estimates ranging from 14 to 30 times the incidence rate observed for chromosomally normal children. Furthermore, one type of leukemia, called {open_quotes}transient leukemia{close_quotes} (TL), occurs almost exclusively in DS infants. The basis of the association between DS and leukemia is unknown, but we and others have hypothesized that it may be influenced by the mechanism of origin of the extra chromosome. Therefore, we initiated a cytogenetic and molecular study of nondisjunction in leukemic DS individuals. To date, we have obtained blood and/or tissue samples from 55 individuals consisting of 17 cases with TL, 7 cases of acute nonlymphocytic leukemia subtype M7 (ANLL-M7, or acute megakaryoblastic leukemia, postulated to be related to TL), and 31 cases of other forms of leukemia. Analysis of these cases suggests differences between DS children with TL and those with other types of leukemia or DS individuals with no history of leukemia. Specifically, the TL and ANLL-M7 cases have a highly significant increase in the frequency of {open_quotes}atypical{close_quotes} constitutional karyotypes (i.e., mosaic trisomies, rings, and/or isochromosomes) and are almost always male. Additionally, genetic mapping studies suggest an increase in the frequency of disomic homozygosity, especially in proximal 21q, in DS individuals with TL and ANLL-M7. 19 refs., 3 figs., 4 tabs.

  10. Leukemic vasculitis: a rare pattern of leukemia cutis.

    PubMed

    Cañueto, Javier; Meseguer-Yebra, Carmen; Román-Curto, Concepción; Santos-Briz, Angel; Fernández-López, Emilia; Fraile, Carmen; Unamuno, Pablo

    2011-04-01

    Although non-specific skin lesions are quite common in patients with leukemia, the specific infiltration of the skin by blast cells, known as leukemia cutis, is rare. Its incidence ranges from 1 to 50% and depends on the specific type of leukemia. Leukemic vasculitis represents a rare form of leukemia cutis consisting of the involvement and destruction of vessel walls by leukemic cells, which in themselves cause the vascular injury. To date, only few cases of leukemic vasculitis have been described. Here, we report two cases of this rare skin condition, one of which mimicked cutaneous polyarteritis nodosa. PMID:20860730

  11. Bryostatin 5 induces apoptosis in acute monocytic leukemia cells by activating PUMA and caspases.

    PubMed

    Wang, Yiwei; Zhang, Jinbao; Wang, Qixia; Zhang, Tao; Yang, Yang; Yi, Yanghua; Gao, Guangxun; Dong, Hongjuan; Zhu, Huafeng; Li, Yue; Lin, Houwen; Tang, Haifeng; Chen, Xiequn

    2013-10-15

    Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the current study, we examined the effects of bryostatin 5 on acute monocytic leukemia cells in vitro and in vivo. We also explored the mechanisms and pathways underlying the increase in apoptosis induced by bryostatin 5. Bryostatin 5 inhibited the growth of primary acute monocytic leukemia cells and U937 cells in a dose- and time-dependent manners. Bryostatin 5 also induced an increase in apoptosis and a decrease in the mitochondrial membrane potential (MMP) in U937 cells. Transmission electron microscopy (TEM) revealed that bryostatin 5-treated cells displayed typical apoptotic characteristics (chromatin condensation, karyopyknosis and formation of crescents and apoptotic bodies). In addition, bryostatin 5 increased the expression of P53 upregulated modulator of apoptosis (PUMA) and slightly increased P53 expression. Bryostatin 5 also significantly decreased Bcl-XL expression and significantly increased the expression levels of Bak, Bax, cleaved caspase 9 and cleaved caspase 3. The pro-apoptotic activity of bryostatin 5 in U937 cells was inhibited by PUMA siRNA and z-LEHD-fmk (a specific caspase 9 inhibitor). In addition, the PUMA siRNA significantly affected the expression of cleaved caspase 9, whereas z-LEHD-fmk had little effect on the expression of PUMA. The results suggest that PUMA is located upstream of caspase 9 in this apoptotic signaling pathway. These novel findings provide mechanistic insight into the induction of apoptosis by bryostatin 5 and might facilitate the development of clinical strategies to enhance the therapeutic efficacy of treatments for acute monocytic leukemia. PMID:24036350

  12. Global characteristics of childhood acute promyelocytic leukemia.

    PubMed

    Zhang, L; Samad, A; Pombo-de-Oliveira, M S; Scelo, G; Smith, M T; Feusner, J; Wiemels, J L; Metayer, C

    2015-03-01

    Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

  13. IRF4 mutations in chronic lymphocytic leukemia.

    PubMed

    Havelange, Violaine; Pekarsky, Yuri; Nakamura, Tatsuya; Palamarchuk, Alexey; Alder, Hansjuerg; Rassenti, Laura; Kipps, Thomas; Croce, Carlo M

    2011-09-01

    Interferon regulatory factor 4 (IRF4) is a member of the interferon regulatory factor family of transcription factors and has been shown to have critical functions at several stages of B-cell development. Genome-wide association study identified a polymorphism in the 3' untranslated region of IRF4 as a chronic lymphocytic leukemia risk locus. In this study, we report a recurrent heterozygous somatic mutation in the DNA-binding domain of IRF4 detected in 7 of 457 chronic lymphocytic leukemia patients (1.5%). Patients with IRF4 mutation have a good prognosis, and 4 of 6 have a trisomy 12. We also found that IRF4 mRNA expression is higher in the patients with the mutation. PMID:21791429

  14. Human Adult T-Cell Leukemia Virus: Complete Nucleotide Sequence of the Provirus Genome Integrated in Leukemia Cell DNA

    Microsoft Academic Search

    Motoharu Seiki; Seisuke Hattori; Yoko Hirayama; Mitsuaki Yoshida

    1983-01-01

    Human retrovirus adult T-cell leukemia virus (ATLV) has been shown to be closely associated with human adult T-cell leukemia (ATL) [Yoshida, M., Miyoshi, I. & Hinuma, Y. (1982) Proc. Natl. Acad. Sci. USA 79, 2031-2035]. The provirus of ATLV integrated in DNA of leukemia T cells from a patient with ATL was molecularly cloned and the complete nucleotide sequence of

  15. The {open_quotes}special employer{close_quotes} issue for nuclear utilities

    SciTech Connect

    Jose, D.E. [Pepper, Hamilton and Sheetz, Philadelphia, PA (United States)

    1992-01-01

    Legal aspects of the Rudenjak versus Jersey Central Power and Light Company lawsuit are summarized in the article. Rudenjak, while working for an independent contractor at the Oyster Creek Nuclear Power Plant, received a 3.335 Rem dose of whole-body radiation over a 4-month period in 1980. In 1988, Rudenjak died of acute leukemia and his widow sued the power company. The utility filed a motion to dismiss based on the statutory employer defense, which was granted by the court; excepts of the court`s decision are included in the article. A similar suit in California is also described; the implication is that legal precedent has been established in California and New Jersey to prevent employees of independent contractors from suing utilities.

  16. Dinosaur Bodies

    NSDL National Science Digital Library

    This lesson plan asks students to think about the ways in which living animals use their bodies and the ways in which dinosaurs might have used their bodies based on fossil evidence and our best educated guesses. These topics serve as a prelude to studying evolution and adaptation.

  17. The Synergistic Repressive Effect of NF-?B and JNK Inhibitor on the Clonogenic Capacity of Jurkat Leukemia Cells

    PubMed Central

    Liu, Xinli; Zhang, Jun; Li, Jing; Volk, Andrew; Breslin, Peter; Zhang, Jiwang; Zhang, Zhou

    2014-01-01

    Deregulation of Nuclear Transcription Factor-?B (NF-?B) and Jun N-terminal kinase (JNK) signaling is commonly detected in leukemia, suggesting an important role for these two signaling pathways in the pathogenesis of leukemia. In this study, using Jurkat cells, an acute T-lymphoblastic leukemia (T-ALL) cell line, we evaluated the effects of an NF-?B inhibitor and a JNK inhibitor individually and in combination on the proliferation, survival and clonogenic capacity of leukemic cells. We found that leukemic stem/progenitor cells (LSPCs) were more sensitive to NF-?B inhibitor treatment than were healthy hematopoietic stem/progenitor cells (HSPCs), as shown by a reduction in the clonogenic capacity of the former. Inactivation of NF-?B leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-?B inhibitor on LSPCs but prevented such repression in HSPCs. Our data suggest that JNK signaling stimulates proliferation/survival in LSPCs but is a death signal in HSPCs. The combination of NF-?B inhibitor and JNK inhibitor might provide a better treatment for T-ALL leukemia by synergistically killing LSPCs while simultaneously preventing the death of normal HPCs. PMID:25526629

  18. FLT3: ITDoes matter in leukemia

    Microsoft Academic Search

    M Levis; D Small

    2003-01-01

    FMS-like tyrosine kinase-3 (FLT3), a receptor tyrosine kinase, is important for the development of the hematopoietic and immune systems. Activating mutations of FLT3 are now recognized as the most common molecular abnormality in acute myeloid leukemia, and FLT3 mutations may play a role in other hematologic malignancies as well. The poor prognosis of patients harboring these mutations renders FLT3 an

  19. Retinoid target genes in acute promyelocytic leukemia

    Microsoft Academic Search

    I Pitha-Rowe; W J Petty; S Kitareewan; E Dmitrovsky

    2003-01-01

    All-trans-retinoic acid (RA)-based differentiation therapy induces clinical remissions in acute promyelocytic leukemia (APL). This has propelled interest in elucidating the molecular mechanisms responsible for these remissions. The t(15;17) rearrangement results in the expression of the PML\\/RAR? fusion transcript that is paradoxically linked to the etiology and clinical retinoid response in APL. PML\\/RAR? expression blocks terminal myeloid differentiation in APL. Treatment

  20. Mast cell leukemia: an extremely rare disease.

    PubMed

    Lu, Dai-Yin; Gau, Jyh-Pyng; Hong, Ying-Chung; Liu, Chun-Yu; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Liu, Jin-Hwang; Chen, Po-Min; Chiou, Tzeon-Jye; Tzeng, Cheng-Hwai

    2014-08-01

    Systemic mastocytosis is characterized by pathologic proliferation and accumulation of mast cells in at least one extracutaneous organ such as liver, spleen, bone marrow, or lymph nodes. The clinical features are highly variable depending on impairment of the involved organ systems. It often raises diagnostic challenges. Here we report a case of a 78-year-old patient with mast cell leukemia. The literature is reviewed regarding the diagnosis and updated management of this rare disease. PMID:25028296

  1. Splenic irradiation in chronic myeloid leukemia.

    PubMed

    Hukku, S; Baboo, H A; Venkataratnam, S; Vidyasagar, M S; Patel, N L

    1983-01-01

    Results of splenic irradiation as the initial and only method of treatment are reported in 25 patients with chronic myeloid leukemia. Peripheral remission was induced in all the patients. Induction was achieved after a short period of 11 to 30 days in the majority of the patients, the longest period being 40 days. Several patients were in remission 9 months after treatment. The results are compared with those obtained by chemotherapy. Some advantages of splenic irradiation over chemotherapy are emphasized. PMID:6305140

  2. Leukemia risk following radiotherapy for breast cancer

    Microsoft Academic Search

    R. E. Curtis; J. D. Jr. Boice; M. Stovall; J. T. Flannery; W. C. Moloney

    1989-01-01

    To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically

  3. B cell acute lymphocytic leukemia in pregnancy

    Microsoft Academic Search

    Justin Bottsford-Miller; Sina Haeri; Arthur M. Baker; Jeremiah Boles; Mark Brown

    2011-01-01

    Acute lymphocytic leukemia (ALL) is a rare occurrence in pregnancy and can be rapidly fatal if left untreated. The need for\\u000a immediate treatment of ALL, coupled with the maternal–fetal risks from the chemotherapy regimen render a therapeutic dilemma\\u000a in pregnant women with ALL. We report a case of ALL diagnosed in the 24th week of pregnancy to outline our management

  4. Leukemia inhibitory factor in human reproduction

    Microsoft Academic Search

    Amir Lass; Weishui Weiser; Alain Munafo; Ernest Loumaye

    2001-01-01

    Objective: To describe the clinical findings, expressions, interactions, and clinical implications of leukemia inhibitory factor (LIF) in human reproduction.Design: Review of published articles.Setting: Clinical development unit of biotechnology company.Intervention(s): None.Result(s): In the endometrium, LIF is expressed in a menstrual cycle–dependent manner, with the highest level occurring at the time of implantation. LIF is also detected in uterine flushing, and its

  5. Therapy of Acute Myelogenous Leukemia in Adults

    Microsoft Academic Search

    Gautam Borthakur; Elihu E. Estey

    \\u000a The clinical and biological heterogeneity of adult acute myelogenous leukemia (AML) is increasingly apparent. Incorporation\\u000a of cytogenetic data into the WHO classification of AML [1] is a testament to the importance of disease biology in treatment\\u000a outcomes. Therefore the approach to treatment of AML in adults need to be based on a risk-stratified approach, the risk being\\u000a that of relapse

  6. E2FBP1 antagonizes the p16INK4A-Rb tumor suppressor machinery for growth suppression and cellular senescence by regulating promyelocytic leukemia protein stability

    PubMed Central

    Fukuyo, Yayoi; Takahashi, Akiko; Hara, Eiji; Horikoshi, Nobuo; Pandita, Tej K; Nakajima, Takuma

    2011-01-01

    Cellular senescence is an irreversible cell cycle arrest triggered by the activation of oncogenes or mitogenic signaling as well as the enforced expression of tumor suppressors such as p53, p16INK4A and promyelocytic leukemia protein (PML) in normal cells. E2F-binding protein 1 (E2FBP1), a transcription regulator for E2F, induces PML reduction and suppresses the formation of PML-nuclear bodies, whereas the down-regulation of E2FBP1 provokes the PML-dependent premature senescence in human normal fibroblasts. Here we report that the depletion of E2FBP1 induces the accumulation of PML through the Ras-dependent activation of MAP kinase signaling. The cellular levels of p16INK4A and p53 are elevated during premature senescence induced by depletion of E2FBP1, and the depletion of p16INK4A, but not p53 rescued senescent cells from growth arrest. Therefore, the premature senescence induced by E2FBP1 depletion is achieved through the p16INK4A-Rb pathway. Similar to human normal fibroblasts, the growth inhibition induced by E2FBP1 depletion is also observed in human tumor cells with intact p16INK4A and Rb. These results suggest that E2FBP1 functions as a critical antagonist to the p16INK4A-Rb tumor suppressor machinery by regulating PML stability. PMID:22010578

  7. Mitochondrial and nuclear DNA phylogeography of Thymallus spp. (grayling) provides evidence of ice-age mediated environmental perturbations in the world's oldest body of fresh water, Lake Baikal

    Microsoft Academic Search

    Mikko T. Koskinen; Igor Knizhin; Craig R. Primmer; Christian Schlotterer; Steven Weiss

    2002-01-01

    Theories on the hydrological history of Lake Baikal, the world's oldest and deepest body of freshwater, and its surrounding great rivers, are currently based solely on geological evidence and are conflicting. Baikal is inhabited by numerous zoogeographical enigmas but their high level of endemism has hindered phylogeographic inferences. We provide a biological perspective of the region's palaeo-hydrological development based on

  8. Acute lymphoblastic leukemia in Weaver syndrome.

    PubMed

    Basel-Vanagaite, Lina

    2010-02-01

    Weaver syndrome comprises pre- and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance and developmental delay; it is a generally sporadic disorder, although autosomal dominant inheritance has been reported. Some of the manifestations characterize both the Weaver and Sotos syndrome, and distinction between the two is mainly by clinical examination and molecular testing. Most of the patients with Sotos syndrome have NSD1 gene deletions or mutations; however, the molecular basis of most of the Weaver syndrome patients is unknown. Patients with overgrowth syndromes have an increased frequency of tumors; the risk in Sotos syndrome patients has been estimated to be about 2-3%, with leukemia and lymphoma accounting for 44% of the malignancies. We report on a 4(1/2)-year-old girl with typical Weaver syndrome who developed acute lymphoblastic leukemia, an association not previously reported, and review the reported cases of Weaver syndrome patients who developed malignancies. Malignancy in Weaver syndrome has been reported previously in six patients. While searching the literature for all reported cases with Weaver syndrome and counting the cases with malignancy, we found that the frequency of tumors or hematologic malignancy was 10.9%. This is likely to be an overestimate, biased by failure to report cases without tumors and by over-reporting cases with this rare association. While the presence of acute lymphoblastic leukemia in our patient might be incidental, we cannot exclude a possible causative association between Weaver syndrome and hematologic malignancy. PMID:20101679

  9. [Expression of Smad4 in leukemia cells].

    PubMed

    Zhang, Yan; Cao, Xu; Jiang, Ming; Ha, Li-Dai; Wen, Bing-Zhao; Li, Ling; Liu, Hui; Zhong, Di; Lin, Ren-Yong; Lu, Xiao-Mei; Feng, Xiao-Hui; Wen, Hao

    2006-08-01

    Loss of transforming growth factor (TGF)-beta signaling has been implicated in malignant transformation of various tissues. Smad4 plays a central role in the signal transduction of TGF-beta. Deletion or mutation of Smad4 has been described in a number of cancers. This study was aimed to investigate a potential role of Smad4 in leukemia including its expression and location in blast cells. The mononuclear cells were separated from bone marrow of leukemia patients. The samples, blast cells of which were more than 90% in mononuclear cells, were selected. The expression and location of Smad4 protein were analyzed by immunohistochemistry methods. The results showed that the Smad4 protein located mainly in nucleus, part of this protein located in cytoplasma, the expressions of Smad4 were not detected in 6 out of 9 ALL patients, in 7 out of 24 AML patients and in 1 out of 2 CML patients; these leukemia patients, in whose cells the expression of Smad4 was not detected, included one L1 and one L3, four L2, one M0, one M1, two M2a, one M3a, one M4b, one M6 and one CML. In conclusion, the Smad4 protein was mainly in nucleus, the deletion or functional change of Smad4 may related with the pathogenesis of human AML. PMID:16928297

  10. [Leptospira, does it simulate or cause leukemia?].

    PubMed

    Velasco-Castrejón, Oscar; Rivas-Sánchez, Beatriz; Gutiérrez, Esther; Chávez, Laura; Duarte, Paulo; Chavarria, Salvador; Rivera-Reyes, Héctor Hugo

    2005-01-01

    Two cases of chronic leptospirosis in bicitopenic and pancitopenic patients, respectively, with mucocutaneous and visceral bleedings were presented. They were diagnosed myeloblastic leukemia M3 and acute lymphoblastic leukemia L2 by bone marrow aspiration and they were treated as such at the hematology department of a general hospital. Both patients died after one of them had considerably improved on being treated with sodium crystalline penicillin at high doses. The histopathological studies could not demonstrate the presence of neoplastic cells in bone marrow but leptospiras were found by means of silver stained preparations (Warthin - Starry) and immunofluorescence, both in this organ and in other tissues studied: kidney., spleen, liver and lungs. The histopathological diagnoses were generalized leptospirosis with medullary aplasia and generalized leptospirosis with myelodisplastic syndrome, respectively. It was reviewed the possibility that leptospira could cause leukemoid syndromes and/or leukemia. Based on these results, it is recommended to hematologists, infectologists, pathologists, and others, to use again the technques of argentic impregnation, immunohystochemistry and immunofluorescence to study the bone marrow and other tissues in order to detect the possible presence of leptospira that would allow to treat the patients more effectively, particularly, patients like these that had serological titres considered negatives so as to avoid the false security existing in the official health institutions about the minimum or null impact that leptospirosis cause in public health, which imply the absence of control systems for this spirochetosis. PMID:17966470

  11. Minimal Residual Disease in Acute Myeloid Leukemia

    PubMed Central

    Hourigan, Christopher S.; Karp, Judith E.

    2014-01-01

    Technological advances in the laboratory have lead to substantial improvements in clinical decision-making by the use of pre-treatment prognostic risk stratification factors in acute myeloid leukemia (AML). Unfortunately similar progress has not been made in treatment response criteria, with the definition of “complete remission” in AML largely unchanged for over half a century. Several recent clinical trials have demonstrated that higher sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission but at increased relapse risk. We review here these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and better clinically utilize MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies such as chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission (mCR) and that recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as a standard of care. PMID:23799371

  12. RIP3 is downregulated in human myeloid leukemia cells and modulates apoptosis and caspase-mediated p65/RelA cleavage

    PubMed Central

    Nugues, A-L; El Bouazzati, H; Hétuin, D; Berthon, C; Loyens, A; Bertrand, E; Jouy, N; Idziorek, T; Quesnel, B

    2014-01-01

    The receptor-interacting protein kinase 3 (RIP3) associates with RIP1 in a necrosome complex that can induce necroptosis, apoptosis, or cell proliferation. We analyzed the expression of RIP1 and RIP3 in CD34+ leukemia cells from a cohort of patients with acute myeloid leukemia (AML) and CD34+ cells from healthy donors. RIP3 expression was significantly reduced in most AML samples, whereas the expression of RIP1 did not differ significantly. When re-expressed in the mouse DA1-3b leukemia cell line, RIP3 induced apoptosis and necroptosis in the presence of caspase inhibitors. Transfection of RIP3 in the WEHI-3b leukemia cell line or in the mouse embryonic fibroblasts also resulted in increased cell death. Surprisingly, re-expression of a RIP3 mutant with an inactive kinase domain (RIP3-kinase dead (RIP3-KD)) induced significantly more and earlier apoptosis than wild-type RIP3 (RIP3-WT), indicating that the RIP3 kinase domain is an essential regulator of apoptosis/necroptosis in leukemia cells. The induced in vivo expression of RIP3-KD but not RIP3-WT prolonged the survival of mice injected with leukemia cells. The expression of RIP3-KD induced p65/RelA nuclear factor-?B (NF-?B) subunit caspase-dependent cleavage, and a non-cleavable p65/RelA D361E mutant rescued these cells from apoptosis. p65/RelA cleavage appears to be at least partially mediated by caspase-6. These data indicate that RIP3 silencing in leukemia cells results in suppression of the complex regulation of the apoptosis/necroptosis switch and NF-?B activity. PMID:25144719

  13. Phenethyl isothiocyanate promotes immune responses in normal BALB/c mice, inhibits murine leukemia WEHI-3 cells, and stimulates immunomodulations in vivo.

    PubMed

    Tsou, Mei-Fen; Tien, Ni; Lu, Chi-Cheng; Chiang, Jo-Hua; Yang, Jai-Sing; Lin, Jing-Pin; Fan, Ming-Jen; Lu, Jang-Jih; Yeh, Su-Peng; Chung, Jing-Gung

    2013-03-01

    Enhanced cruciferous vegetable consumption is associated with the reduction of cancer incidence as shown in epidemiological studies. Phenethyl isothiocyanate (PEITC), one of the important compounds in cruciferous vegetables, has been shown to induce apoptosis in many types of human cancer cell lines, but there is no available information addressing the effects on normal and leukemia mice in vivo. The purpose of this study is to focus on the in vivo effects of PEITC on immune responses of normal and WEHI-3 leukemia BALB/c mice in vivo. Influences of PEITC on BALB/c mice after intraperitoneal (i.p.) injection with WEHI-3 cells and normal mice were investigated. In normal BALB/c mice, PEITC did not affect the body weight when compared to the olive oil treated animals. Moreover, PEITC promoted phagocytosis by macrophages from peripheral blood mononuclear cells (PBMC) and peritoneal cavity, increased the levels of CD11b and Mac-3, decreased the level of CD19 and promoted natural killer (NK) cell cytotoxic activity, but it did not alter the level of CD3. Also, PEITC enhanced T cell proliferation after concanavalin A (Con A) stimulation. Otherwise, PEITC increased the body weight, but decreased the weight of liver and spleen as compared to the olive oil-treated WEHI-3 leukemia mice. PEITC also increased the level of CD19, decreased the levels of CD3 and Mac-3 rather than influence in the level of CD11b, suggesting that the differentiation of the precursor of macrophages and T cells was inhibited, but the differentiation of the precursor of B cells was promoted in leukemia mice. Furthermore, PEITC enhanced phagocytosis by monocytes and macrophages from PBMC and peritoneal cavity, and also promoted the NK cell cytotoxic activity in comparison with the group of leukemia mice. Based on these observations, the biological properties of PEITC can promote immune responses in normal and WEHI-3 leukemia mice in vivo. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013. PMID:21626647

  14. MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-04

    Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  15. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  16. Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute myeloid leukemia cells in vitro

    PubMed Central

    Li, Fei-fei; Yi, Sha; Wen, Lu; He, Jing; Yang, Li-jing; Zhao, Jie; Zhang, Ben-ping; Cui, Guo-hui; Chen, Yan

    2014-01-01

    Aim: Skewed cytoplasmic accumulation of NPM mutant protein (NPM1c+) is close related to leukemia pathogenesis. The aim of this study was to investigate whether oridonin, a diterpenoid isolated from the Chinese traditional medicine Rabdosia rubescens, was able to interfere with NPM1c+ protein trafficking and induce apoptosis in NPM1c+ acute myeloid leukemia cells in vitro. Methods: OCI-AML3 cell line harboring a NPM1 gene mutation was examined. Cell growth was detected by MTT assay. Cell apoptosis was evaluated using flow cytometry and Hoechst 33258 staining. The expression and subcellular localization of relevant proteins were detected by Western blot and immunofluorescent staining. The mRNA expression was detected by RT-PCR. Results: Oridonin (2–12 ?mol/L) dose-dependently inhibited the viability of OCI-AML3 cells (the IC50 value was 3.27±0.23 ?mol/L at 24 h). Moreover, oridonin induced OCI-AML3 cell apoptosis accompanied by activation of caspase-3 and nuclear translocation of NPM1c+ protein. Oridonin did not change the expression of Crm1 (the export receptor for nuclear export signal-containing proteins), but induced nuclear translocation of Crm1. Oridonin markedly increased the expression of nucleoporin98 (Nup98), which had an important role in Crm1-mediated nuclear protein export, and induced nuclear accumulation of Nup98. Furthermore, oridonin markedly increased the expression of p14arf and p53. Conclusion: In NPM1c+ leukemia cells, oridonin induces NPM1c+ protein translocation into the nucleus possibly via nuclear accumulation of Crm1; the compound markedly increases p53 and p14arf expression, which may contribute to cell apoptosis. PMID:24902788

  17. Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-04-06

    Acute Leukemias of Ambiguous Lineage; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  18. Body Swatter

    NSDL National Science Digital Library

    2013-02-15

    Students work in cooperative groups to research and write questions for an active game designed to review the major organs of the systems of the human body (digestive, respiratory, circulatory, and excretory system).

  19. ?-Arrestin1 promotes the self-renewal of the leukemia-initiating cell-enriched subpopulation in B-lineage acute lymphoblastic leukemia related to DNMT1 activity.

    PubMed

    Shu, Yi; Zhou, Xiaoyan; Qi, Xinkun; Liu, Shan; Li, Kang; Tan, Junjie; Liu, Zhidai; Yu, Jie; Zhang, Penghui; Zou, Lin

    2015-02-01

    The self-renewal ability of the leukemia initiating cell-enriched subpopulation is critical for leukemia initiation and maintenance. However, the regulation of leukemia initiating cells for the leukemia progression is poorly understood. In this study, we observed that ?-Arrestin1, a multiple-function protein, is elevated in leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients. The loss of ?-Arrestin1 in leukemia initiating cells-enriched fraction attenuates its self-renewal capacity both in vitro and in vivo. Further experiments showed that the mRNA expression level of ?-Arrestin1 is negatively correlated with that of PTEN in leukemia initiating cells-enriched fraction. Moreover, DNA methylation of the PTEN promoter region, the activity and expression of DNMTs were enhanced in the leukemia initiating cells-enriched fraction. The inhibition of DNMT1 activity impaired the self-renewal and increased expression of PTEN of leukemia initiating cells-enriched fraction. In addition, depletion of ?-Arrestin1 significantly decreased DNMT1 activity and PTEN methylation, and consistently increased PTEN expression in leukemia initiating cells-enriched fraction. Our study reveals a novel function of ?-Arrestin1 in the regulation of the self-renewal of leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients related to DNMT1 activity, indicating that ?-Arrestin1 is a potential therapeutic target in B-lineage acute lymphoblastic leukemia. PMID:25444908

  20. Role of Promyelocytic Leukemia (PML) Protein in Tumor Suppression

    Microsoft Academic Search

    Eduardo M. Rego; Zhu-Gang Wang; Daniela Peruzzi; Le-Zhen He; Carlos Cordon-Cardo; Pier Paolo Pandolfi

    The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor a (RAR a ) gene in the vast majority of acute promyelocytic leukemia (APL) patients as a consequence of chromo- somal translocations. The PMLRAR a oncoprotein is thought to antagonize the function of PML through