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1

Hairy cell leukemia  

Microsoft Academic Search

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder characterized by pancytopenia and variable infiltration\\u000a of the reticuloendothelial system with “hairy” lymphocytes. HCL is more common in men than women and has a median age of diagnosis\\u000a of 52 yr. Typically, patients with HCL respond well to purine analog-based therapy. The purpose of this review will be to\\u000a establish

Ronan Swords; Francis Giles

2007-01-01

2

[Recurrent somatic mutation in hairy cell leukemia].  

PubMed

Hairy cell leukemia is a mature B-cell non-Hogkin lymphoma characterized by unique clinical, morphological and immunhistochemical features. Patients with hairy cell leukemia usually present with splenomegaly, progressive pancytopenia and a relative indolent clinical course. The diagnosis does not always indicate immediate treatment, as treatment depends on the clinical stage of the leukemia. Asymptomatic disease without progression requires a watchful waiting policy, while other categories usually need treatment. The treatment of choice is purine nucleoside analogues (pentostatin, cladribine) which can achieve complete remission even for decades. Interferon and monoclonal CD20 antibodies can also significantly prolong event-free survival. Unfortunately, only the latter two therapies are easily available in Hungary. Splenectomy, which was suggested as first line treatment before the era of purine nucleoside analogues, is only recommended as a last resort. Although hairy cell leukemia is a well-defined lymphoproliferative disease, sometimes it is difficult to differentiate it from other similar entities such as hairy cell leukema variant, splenic marginal zone lymphoma, small lymphocytic lymphoma etc. Making the correct diagnosis is of utmost importance because of the great difference in treatment modalities. Recently, a somatic mutation was found in all analysed hairy cell leukemia samples, but not in other splenic B-cell lymphomas. This article reviews the significance of this observation and presents the different types of methods for the detection of this mutation. PMID:23335721

Sári, Eszter; Nagy, Zsolt; Demeter, Judit

2013-01-27

3

PRAME expression in Hairy Cell Leukemia  

PubMed Central

PRAME has been proposed as a useful marker for solid tumors and acute B-cell malignancies. Several studies demonstrate expression in CLL. To further examine its B-cell tumor distribution, we studied PRAME in both CLL and hairy cell leukemia (HCL). While by conventional PCR only 8% of 37 HCL and 27% of 22 CLL patients were positive, nearly all patients and normal donors expressed PRAME by real-time quantitative (TaqMan) PCR. We conclude that HCL and CLL differ in PRAME overexpression, and that basal normal expression of PRAME may limit its usefulness for following patients with minimal residual CLL or HCL.

Arons, Evgeny; Suntum, Tara; Margulies, Inger; Yuan, Constance; Stetler-Stevenson, Maryalice; Kreitman, Robert J.

2008-01-01

4

Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia  

MedlinePLUS

... note these links take you to other sections: ASCO Answers Fact Sheet : Read a one-page fact ... Video : View a short video led by an ASCO expert in leukemia that provides basic information and ...

5

[Complete remission after Rituximab treatment in refractory hairy cell leukemia].  

PubMed

A 40 year-old man with hairy cell leukemia (HCL) was treated with Cladribin, but achieved only partial response (PR). As expected, both 2 and 5 years later the disease had progressed and the patient was therefore twice retreated with Cladribin. A bone marrow examination after the last Cladribin course showed complete response with residual disease (CR-RD). The patient received consolidation therapy with Rituximab, achieved complete response (CR) and was still in CR 9 months later. Rituximab is a good treatment option for patients with refractory HCL because of its significant activity and minimal toxicity. PMID:18570771

Petruskevicius, Irma; Bukh, Anne; Mertz, Henrik; Johnsen, Hans Erik

2008-06-23

6

Bone Marrow Histological Modifications Induced by Alpha Interferon in Hairy Cell Leukemia  

Microsoft Academic Search

This paper reports the bone marrow histological picture in 7 patients with hairy cell leukemia treated with recombinant interferon. Bone marrow biopsies were performed at diagnosis, after 1, 3 and 7 months from the beginning of treatment and at 12 months at treatment suspension. The main modifications observed were a conspicuous reduction of hairy cell infiltrate, profound hypoplasia induced by

G. Lambertenghi-Deliliers; E. Benazzi; A. Cortelezzi; E. E. Polli

1987-01-01

7

Disseminated sporotrichosis in a patient with hairy cell leukemia treated with amphotericin B and posaconazole.  

PubMed

We describe a case of disseminated Sporothrix schenckii infection in a man with underlying hairy cell leukemia. The immunological defects associated with this malignancy, as well as the management of refractory sporotrichosis are reviewed. PMID:21612561

Bunce, Paul E; Yang, Lin; Chun, Soohun; Zhang, Sean X; Trinkaus, Martina A; Matukas, Larissa M

2011-05-26

8

Evidence of canonical somatic hypermutation in hairy cell leukemia  

PubMed Central

To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition.

Arons, Evgeny; Roth, Laura; Sapolsky, Jeffrey; Suntum, Tara; Stetler-Stevenson, Maryalice

2011-01-01

9

Treatment of hairy-cell leukemia with chemoradiotherapy and identical-twin bone-marrow transplantation  

SciTech Connect

A patient with progressive hairy-cell leukemia and a normal genetically identical twin presented an opportunity to determine the sensitivity of this disease to high-dose alkylating-agent chemotherapy and total-body irradiation, since the marrow aplasia induced could potentially be overcome by reconstitution with normal marrow stem cells from the twin. After such therapy the patient rapidly recovered normal marrow function with no evidence of infiltrating hairy cells; he is still in complete remission four years after transplantation. In contrast to other patients with this disorder, he has had no predisposition to infections since transplantation. These results demonstrate that hairy-cell leukemia is sensitive to high-dose cytotoxic therapy and is not associated with any microenvironmental abnormalities that prevent repopulation with normal stem cells. Thus, high-dose chemoradiotherapy followed by bone-marrow transplantation is an effective and potentially curative therapy for hairy-cell leukemia. (JMT)

Cheever, M.A. (Univ. of Washington, Seattle); Fefer, A.; Greenberg, P.D.; Appelbaum, F.; Armitage, J.O.; Buckner, C.D.; Sale, G.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.

1982-08-01

10

CD200 Flow Cytometric Assessment and Semiquantitative Immunohistochemical Staining Distinguishes Hairy Cell Leukemia From Hairy Cell Leukemia-Variant and Other B-Cell Lymphoproliferative Disorders.  

PubMed

Objectives: To evaluate CD200 expression in B-cell proliferative disorders. Methods: We analyzed 180 recent specimens of B-cell neoplasms for CD200 expression by flow cytometric immunophenotypic analysis, which is better able to assess relative intensity of staining than immunohistochemical staining. Results: We found that hairy cell leukemia exhibits a high level of staining for CD200 in comparison to other B-cell lymphoproliferative disorders, including hairy cell leukemia-variant (HCL-V), marginal zone lymphoma, and lymphoplasmacytic lymphoma. We confirmed this observation by semiquantitative immunohistochemical staining. Conclusions: Assessment of the CD200 expression level is helpful to distinguish HCL from HCL-V and other B-cell lymphoproliferative disorders and in the differential diagnosis of B-cell neoplasms in general. PMID:24045551

Pillai, Vinodh; Pozdnyakova, Olga; Charest, Karry; Li, Betty; Shahsafaei, Aliakbar; Dorfman, David M

2013-10-01

11

Hairy cell leukemia: A B-lymphocytic disorder derived from splenic marginal zone lymphocytes?  

Microsoft Academic Search

Although there is increasing evidence that the majority of cases of hairy cell leukemia represent B-lymphoproliferative disorders, the exact subset of B-cells from which hairy cells are derived, is still unclear. On the basis of results obtained in previous studies, and data collected from the literature, it is suggested that B-lymphocytes normally residing in the marginal zone of the splenic

J. J. van den Oord; C. de Wolf-Peeters; V. J. Desmet

1985-01-01

12

Immunohistochemical evaluation of bone marrow involvement in hairy cell leukemia during interferon therapy  

Microsoft Academic Search

Bone marrow biopsies from 7 patients afflicted with hairy cell leukemia were studied with a panel of monoclonal antibodies at different intervals during alpha recombinant interferon therapy. Monoclonal antibodies Dako-LC and F 8.11.13 were used because they are highly reactive with hairy cells, and 82 H 3 and LeuM 1 were also utilized to identify respectively the residual hemopoietic and

D. Soligo; G. Lambertenghi-Deliliers; E. Berti; N. Polli; E. E. Polli

1987-01-01

13

Hairy cell leukemia in a patient with situs inversus totalis: an extremely rare combination.  

PubMed

Hairy cell leukemia is a rare cancer of the blood. The occurrence of hairy cell leukemia with another very rare genetic disorder makes us question whether it is just a coincidence. This article reports the first case of hairy cell leukemia in a patient with situs inversus totalis in western literature. There have been studies into the pathogenesis of situs inversus totalis that suggest it is caused by the failure of embryonic cells to properly rotate during embryogenesis. On the molecular level, the nodal cilia, which are responsible for embryonic rotation, are built by transport through the KIF3 complex - a kinesin superfamily of molecular motors. The KIF3 complex is also responsible for N-cadherin movement in cells. Furthermore, it is well known that these cell adhesion molecules play an important role in carcinogenesis and its progression. This report attempts to link the rare conditions and propose a possible genetic relationship between the two. PMID:23647303

Pathak, Prajwol; Zilberman, Valeria; Avezbakiyev, Boris; Gotlieb, Vladimir

2013-05-01

14

Classical Hairy Cell Leukemia and Its Variant: A 17Year Retrospective Survey in Taiwan Chinese  

Microsoft Academic Search

Background: Classical hairy cell leukemia (HCL-C) and its variant (HCL-V) are rare chronic B-cell lymphoproliferative disorders. Only a few reports in Chinese patients are available. Methods: We retrospectively reviewed 16 patients with HCL-C and HCL-V in Taiwan over a 17-year period. Results: Eight were HCL-C and 8 were HCL-V. All HCL accounted for 0.7% of all adult leukemias. Compared to

Hsiao-Wen Kao; Po Dunn; Ming-Chung Kuo; Lee-Yung Shih; Tung-Liang Lin; Jin-Hou Wu; Tzung-Chih Tang; Hung Chang; Hong-Cheng Wu; Yu-Shin Hung

2011-01-01

15

Primary treatment of hairy cell leukemia: Should IFN-therapy replace splenectomy?  

Microsoft Academic Search

Hairy cell leukemia (HCL) was described first in 1958 by Bouroncle [2] in a patient who had the disease for more than 30 years. The disorder, initially named leukemic reticulo-endotheliosis is a distinct clinical-pathological entity. Important aspects of this disease have recently been published in two issues (Seminars in Oncology Dec. 1984) summarizing the results of a workshop held at

F. Porzsolt

1986-01-01

16

Leukemic meningitis in a patient with hairy cell leukemia. A case report  

SciTech Connect

Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms.

Wolfe, D.W.; Scopelliti, J.A.; Boselli, B.D.

1984-09-15

17

Double IgA bands in serum from a patient with lymphoplasmacytoid leukemia with hairy-cell morphology.  

PubMed

We present a case of plasmacytoid lymphocytic leukemia with hairy-cell-like cytoplasmic projections and separate monomeric and polymeric IgA(lambda) serum bands confirmed by immunofixation. After a prolonged initial good response to chemotherapy, the patient had recurrent disease with increased plasmacytoid blastic feature and died. The relationship of this case to B-cell proliferative disorders is discussed. PMID:3690865

Loo, S Y; Bhagavan, N V; Scottolini, A G

1987-12-01

18

High levels of circulating soluble receptors for tumor necrosis factor in hairy cell leukemia and type B chronic lymphocytic leukemia.  

PubMed Central

The presence of soluble tumor necrosis factor (TNF) binding proteins (BP) was investigated in the sera of healthy volunteer blood donors and cancer patients. Two distinct types of TNFBP, types A and B, which are immunologically related to the cellular 75-kD TNF receptor (TNFR) and the cellular 55-kD TNFR, respectively, were assessed by immunoassays using nonblocking anti-receptor antibodies and 125I-recombinant human TNF alpha. As compared to the titers observed in 25 healthy controls, TNFBP types A and B titers were found to be elevated in almost all sera obtained from patients with underlying malignant disease. The highest amounts of TNFBP were seen in the sera of patients with B cell malignancies including hairy cell leukemia (HCL) and type B chronic lymphocytic leukemia. Treatment of HCL patients with recombinant human interferon-alpha was associated with decrease of circulating TNFBP.

Digel, W; Porzsolt, F; Schmid, M; Herrmann, F; Lesslauer, W; Brockhaus, M

1992-01-01

19

Minimal Residual Disease May Predict Bone Marrow Relapse in Patients With Hairy Cell Leukemia Treated With 2-Chlorodeoxyadenosine  

Microsoft Academic Search

Minimal residual disease (MRD) can be detected in bone marrow core biopsies of patients with hairy cell leukemia (HCL) after treatment with 2-chlorodeoxyadenosine (2-CdA) using immunohistochemical (IHC) techniques. The purpose of this study was to determine whether the presence of MRD predicts bone marrow relapse. We studied paraffin- embedded bone marrow core biopsies from 39 patients with HCL in complete

Susan Wheaton; Martin S. Tallman; David Hakimian; LoAnn Peterson

1996-01-01

20

Interleukin-6 functions as an intracellular growth factor in hairy cell leukemia in vitro.  

PubMed Central

The role of interleukin-6 (IL-6) in the growth of B cell derived hairy cell leukemia (HCL) was characterized. Purified hairy cells (HCs) did not increase DNA synthesis in vitro in response to exogenous IL-6; however, they expressed IL-6 receptor (IL-6R) mRNA and bound directly fluorochrome labeled IL-6. IL-6 mRNA was not detectable in tumor cells by Northern blotting, but was evident using PCR amplification. Although intracytoplasmic IL-6 protein was not demonstrable, HCs did secrete low levels of IL-6. Neutralizing antibody to IL-6 did not inhibit HC DNA synthesis. Since tumor necrosis factor (TNF) is a growth factor for HCL, we determined whether the TNF effect could be IL-6-mediated. TNF markedly augmented in vitro DNA synthesis by HCs. TNF did not alter IL-6R expression or IL-6 binding; however, IL-6 mRNA and IL-6 protein were detectable after 3-d culture of HCs with TNF. In addition, IL-6 secretion by HCs was markedly augmented by TNF. Finally, although neither IL-6 nor anti-IL-6 antibody altered TNF-induced DNA synthesis by HCs, IL-6 antisense oligonucleotide inhibited TNF-induced DNA synthesis and IL-6 secretion by HCs. Therefore, IL-6 does not directly affect the growth of HCL, but rather mediates TNF-induced DNA synthesis via an intracytoplasmic mechanism. Images

Barut, B; Chauhan, D; Uchiyama, H; Anderson, K C

1993-01-01

21

Hairy cell leukemia in kidney transplantation: lesson from a rare disorder  

PubMed Central

We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious/EBV-related proliferative stimuli. To date, HCL has not been considered among PTLDs. Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase. Such a biochemical link between the oncogene-dependent signaling and calcineurin inhibitor activities suggests that HCL in transplanted patients might be a peculiar type of PTLD based on the presence of a specific mutation. This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer.

2013-01-01

22

Synchronous Detection of Hairy Cell Leukemia and HIV-Negative Kaposi's Sarcoma of the Lymph Node: A Diagnostic Challenge and a Rare Coincidence.  

PubMed

Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder and accounts for around 2% of all forms of leukemias. The association of HCL with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and Kaposi's sarcoma is rare, with only few cases of such an association having been reported. We describe a 42-year-old male patient with a well characterized HCL and in whom HIV-negative Kaposi's sarcoma of the lymph node was detected. PMID:22087095

Aydin, Seniz Ongoren; Eskazan, Ahmet Emre; Aki, Hilal; Ozguroglu, Mustafa; Baslar, Zafer; Soysal, Teoman

2011-09-03

23

Synchronous Detection of Hairy Cell Leukemia and HIV-Negative Kaposi's Sarcoma of the Lymph Node: A Diagnostic Challenge and a Rare Coincidence  

PubMed Central

Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder and accounts for around 2% of all forms of leukemias. The association of HCL with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and Kaposi's sarcoma is rare, with only few cases of such an association having been reported. We describe a 42-year-old male patient with a well characterized HCL and in whom HIV-negative Kaposi's sarcoma of the lymph node was detected.

Aydin, Seniz Ongoren; Eskazan, Ahmet Emre; Aki, Hilal; Ozguroglu, Mustafa; Baslar, Zafer; Soysal, Teoman

2011-01-01

24

Indium 111-labeled platelet kinetic studies and platelet-associated IgG in hairy cell leukemia  

SciTech Connect

In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous /sup 111/In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of /sup 111/In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of /sup 111/In-labeled platelets in nonsplenectomized patients suggests hypersplenism with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.

Panzer, S.; Lechner, K.; Neumann, E.; Meryn, S.; Haubenstock, A.

1986-07-15

25

Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature.  

PubMed

Comparative expressed sequence hybridization (CESH) to chromosomes is a recently introduced technique that identifies chromosomal regions corresponding to a differential gene expression. This technique is analogous to comparative genomic hybridization (CGH) that detects genomic imbalances. We applied CESH for the study of hairy cell leukemia (HCL), a disorder with a largely unknown expression profile. Twelve HCL cases with spleen involvement were investigated by CESH and CGH. While the latter analysis identified only a few nonrecurrent genomic imbalances, CESH showed a consistent expression profile in all HCL cases. In addition, pairing normal spleen with normal lymph node, a "spleen signature" was established by CESH. This signature most likely reflects the expression profile of spleen-specific components, such as the sinusoidal lining cells from the red pulp and the marginal zone B cells from the white pulp. Imprint of the spleen signature was found in the HCL expression profile, suggesting that HCL may originate from a particular B-cell subset present in these splenic components. Besides pairing HCL with normal lymph node and spleen, we identified an "HCL signature" comprising several chromosome regions with altered expression. The most significantly underexpressed regions include 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24; and 13q31 and Xq13.3-q21 were the most significantly overexpressed. These regions possibly harbor genes related to the biology and the pathogenesis of HCL. Their identification warrants further molecular investigations. PMID:15016649

Vanhentenrijk, Vera; De Wolf-Peeters, Chris; Wlodarska, Iwona

2004-03-11

26

A New Subtype of Human T-Cell Leukemia Virus (HTLV-II) Associated with a T-Cell Variant of Hairy Cell Leukemia  

Microsoft Academic Search

Human T-cell leukemia virus (HTLV) is a human type-C RNA tumor virus (retrovirus) previously identified in and isolated from several patients with T-cell leukemias or lymphomas. The known virus isolates from the United States and Japan are closely related and are found in adults with an acute malignancy of mature T cells. A related retrovirus has been found in a

V. S. Kalyanaraman; M. G. Sarngadharan; Marjorie Robert-Guroff; Isao Miyoshi; Douglas Blayney; David Golde; Robert C. Gallo

1982-01-01

27

The Monoclonal Antibodies aS-HCL 1 (aLeu-14) and aS-HCL 3 (aLeu-M5) Allow the Diagnosis of Hairy Cell Leukemia  

Microsoft Academic Search

To define cell surface antigens associated with hairy cell leukemia (HCL). and to gain better insight into the origin of this disease. we developed monoclonal antibodies against spleen cells of a patient with this disease. Although none of these antibodies alone proved specific for the leukemic cells. two of them. designated aS-HCL 1 (aLeu-14) and aS-HCL 3 (aLeu-M5) were found

Roland Schwarting; Harald Stein; Chang Yi

1985-01-01

28

Treating Hairy Cell Leukemia  

MedlinePLUS

... Treatment is most often with one of the purine analog drugs -- either cladribine (2-CdA) or pentostatin. ... it will most be often treated with a purine analog again. Often the same drug will be ...

29

Evolving concepts in the pathogenesis of hairy-cell leukaemia  

Microsoft Academic Search

Hairy-cell leukaemia (HCL) has long been recognized as distinct from other chronic B-cell malignancies, but several questions remain unanswered. What is the HCL cell of origin? Why does HCL lack the hallmarks of most mature B-cell tumours (for example, chromosomal translocations and consistent lymph node involvement) and show unique features like 'hairy' morphology and bone-marrow fibrosis? Gene-expression profiling and other

Arcangelo Liso; Miguel Piris; Enrico Tiacci; Brunangelo Falini

2006-01-01

30

Occupational exposure to solvents and hairy cell leukaemia  

PubMed Central

OBJECTIVES: The role of occupational exposures in hairy cell leukaemia was investigated through a multicentre, hospital based, case-control study. This paper analyses the role of exposure to solvents other than benzene in hairy cell leukaemia. METHODS: The study included 226 male cases and 425 matched controls, exposure to solvents was evaluated by expert case by case review of the detailed data on occupational exposures generated by specific interviews. Also, exposure to solvents was evaluated with an independently constructed job exposure matrix (JEM). RESULTS: No association was found between hairy cell leukaemia and previous employment in a job exposed to solvents (odds ratio (OR) 0.9 95% confidence interval (95% CI) 0.6 to 1.3). ORs for the main occupational tasks exposed to solvents were around 1 and did not increase with the frequency or the duration of the tasks. No specific type of paint or glue was found to be significantly associated with hairy cell leukaemia. No association was found with exposure to solvents, taken as a whole, with either expert assessments or the JEM. No association was found with aromatic, chlorinated, or oxygenated subgroups of solvents. The ORs did not increase with the average intensity of exposure assessed by the experts, with the frequency of use, or with the duration of exposure. Finally, no association was found with non-occupational exposure to solvents. CONCLUSIONS: The study did not show any association between exposure to solvents and hairy cell leukaemia.  

Clavel, J.; Mandereau, L.; Conso, F.; Limasset, J. C.; Pourmir, I.; Flandrin, G.; Hemon, D.

1998-01-01

31

Leukemia Stem Cells  

Microsoft Academic Search

\\u000a Normal hematopoiesis develops hierarchically from a hematopoietic stem cell, which is defined by both extensive self-renewal\\u000a capacity and multi-lineage potential, i.e. the ability to give rise to fully differentiated cells of all hematopoietic lineages.\\u000a Since leukemia can be considered as malignant hematopoiesis, the existence of a developmental hierarchy in leukemia with a\\u000a malignant stem cell at its apex was postulated

Markus Müschen

32

Acute and Chronic Leukemia: Diagnosis, Treatment.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1979-01-01

33

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia  

ClinicalTrials.gov

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic 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 Grade III Lymphomatoid Granulomatosis; 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; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

2013-09-11

34

Leukemia blast-induced T-cell anergy demonstrated by leukemia-derived dendritic cells in acute myelogenous leukemia  

Microsoft Academic Search

ObjectiveTo elucidate the mechanism of immunologic escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we attempted to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia-derived dendritic cells, we investigated leukemia cell-associated T-cell anergy.

Miwako Narita; Masuhiro Takahashi; Aichun Liu; Kohji Nikkuni; Tatsuo Furukawa; Ken Toba; Satoru Koyama; Kazue Takai; Masayoshi Sanada; Yoshifusa Aizawa

2001-01-01

35

Diagnosis and Treatment of Acute and Chronic Leukemia.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1978-01-01

36

Diagnosis and Treatment of Acute and Chronic Leukemia.  

National Technical Information Service (NTIS)

The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other ne...

1977-01-01

37

Structural characterization of pectic hairy regions isolated from apple cell walls  

Microsoft Academic Search

Cell wall pectic substances have a great influence on the production and quality aspects of apple juice. Apple juices were characterized by their polysaccharide content and composition. A pectic fraction, retained by ultrafiltration of a liquefaction juice, was isolated and termed MHR (modified hairy regions). MHR, resistant to further enzymic degradation by the liquefaction enzymes, was characterized using chemical and

H. A. Schols

1995-01-01

38

"Hairy Baskets" Associated with Degenerative Purkinje Cell Changes in Essential Tremor  

PubMed Central

Essential tremor (ET) is one of the most common neurological diseases. Increased numbers of torpedoes and Purkinje cell loss have been documented in the brains of patients with ET. We recently observed a dense and tangled appearance (“hairiness”) of the basket cell axonal plexuses that surround Purkinje cell soma in Bielschowsky preparations of cerebellar cortex in ET brains. Here, we assessed basket cell “hairiness” in 37 ET (32 cerebellar ET; 5 Lewy body variant ET [LBVET]), 21 non-disease control, and 48 disease control brains using a semiquantitative scale. In 8 cerebellar ET cases (25%) there were high basket scores (rating = 3), whereas no LBVET, 1 non-disease control (4.8%) and 2 diseased controls (4.2%) had high basket scores (p = 0.001). The hairy basket scores correlated with numbers of torpedoes (p < 0.001) and inversely with numbers of Purkinje cells (p = 0.06). Axonal plexus density obtained by image analysis of basket cell processes traced from digitized images was higher in ET than in non-diseased control cases (p = 0.016). Closely spaced sites of synaptic contact between basket cell processes and Purkinje cells were identified by electron microscopy in ET cases. These data indicate that structural changes are not restricted to Purkinje cells in ET and that other neurons within their functional network may be involved in its pathogenesis.

Erickson-Davis, Cordelia; Faust, Phyllis L.; Vonsattel, Jean-Paul G.; Gupta, Sachin; Honig, Lawrence S.; Louis, Elan D.

2010-01-01

39

Scientists Report Complete Remissions in Early Leukemia Trial  

Cancer.gov

Scientists report in the New England Journal of Medicine that 11 of 13 patients with hairy cell leukemia, a cancer of the immune system, had complete remissions after receiving adequate treatment with the recombinant immunotoxin BL22

40

Effects of cycloartane saponins from hairy roots of Astragalus membranaceus Bge., on human tumor cell targets  

Microsoft Academic Search

For the first time three different natural compounds, isolated from hairy roots of Astragalus membranaceus, cultivated in airlift bioreactor were tested for their cytotoxic potential and apoptosis induction in a panel of human tumor cell lines. Root cultures, cultivated in bioreactor gave 18.5gl?1 dry wt roots with the highest astragaloside production in vitro up to now — 1.64% (astragaloside I),

I. Ionkova; G. Momekov; P. Proksch

2010-01-01

41

Acute myeloid leukemia: leukemia stem cells write a prognostic signature  

Microsoft Academic Search

In a recent interesting article, analysis of gene expression between phenotypically defined acute myeloid leukemia (AML) leukemia\\u000a stem cells (LSCs) and more mature leukemia progenitor cells is used to generate a differentially expressed gene signature\\u000a for LSCs. Through clever bioinformatic weighting analysis, the authors describe a method to convert this signature into a\\u000a single score for any given sample and

Emma J Gudgin; Brian JP Huntly

2011-01-01

42

Effects of cycloartane saponins from hairy roots of Astragalus membranaceus Bge., on human tumor cell targets.  

PubMed

For the first time three different natural compounds, isolated from hairy roots of Astragalus membranaceus, cultivated in airlift bioreactor were tested for their cytotoxic potential and apoptosis induction in a panel of human tumor cell lines. Root cultures, cultivated in bioreactor gave 18.5 g l(-1) dry wt roots with the highest astragaloside production in vitro up to now - 1.64% (astragaloside I), 1.12% (astragaloside II) and 1.08% (astragaloside III). In this manner the production in airlift bioreactor can be used as means of reliable supply of cycloartane saponins to extend the research to human clinical studies. PMID:20060881

Ionkova, I; Momekov, G; Proksch, P

2010-01-10

43

A paraneoplastic membranoproliferative glomerulonephritis with isolated C3 deposits associated with hairy cell leukaemia.  

PubMed

We describe a 35-year-old woman who presented with proteinuria and microscopic haematuria. Blood tests revealed a low C3 complement level, with no evidence of cryoglobulin. Renal biopsy showed a Type 1 membranoproliferative glomerulonephritis (MPGN) with isolated C3 deposits on immunofluorescence study. Bone marrow aspirate, done for monocytopenia, was consistent with a diagnosis of hairy cell leukaemia (HCL). Both haematological and nephrological diseases completely responded to treatment with cladribine, strongly suggesting that the renal disease was a paraneoplastic syndrome. To our knowledge, this is the first report of a non-cryoglobulinaemic MPGN associated to HCL. PMID:20335271

Abboud, Imad; Galicier, Lionel; De Labarthe, Adrienne; Dossier, Antoine; Glotz, Denis; Verine, Jérôme

2010-03-24

44

Human Lyb-2 homolog CD72 is a marker for progenitor B-cell leukemias.  

PubMed

S-HCL 2 is the prototype antibody of the recently defined CD72 cluster (human Lyb-2). Under nonreducing conditions, S-HCL 2 monoclonal antibody (mAb) precipitates a glycoprotein of 80-86 kDa. Under reducing conditions, a dimer of 43 and 39 kDa, with core proteins of 40 and 36 kDa, is precipitated. CD72 expression in normal and malignant tissues is different from expression of all other previously described human B-cell antigens. In peripheral blood and bone marrow, the antigen appears to be present on all B lymphocytes, with the exception of plasma cells. In tissue, immunohistochemical staining revealed positivity for all known B-cell compartments; however, pulpa macrophages of the spleen and von Kupffer cells exhibited distinct positivity for CD72 also. Among 83 malignant non-Hodgkin's lymphomas examined by immunohistochemistry (alkaline phosphatase anti-alkaline phosphatase technique), all 54 B-cell lymphomas, including precursor B-cell lymphomas, Burkitt's lymphomas, germinal center lymphomas, chronic lymphocytic leukemias, and hairy cell leukemias, were CD72 positive, but no T-cell lymphomas were. Flow cytometry study of more than 80 mainly acute leukemias (52 B-cell leukemias) showed reactivity with S-HCL 2 mAb over the full range of B-cell differentiation. In particular, very early B cells in cytoplasmic Ig (cIg)-negative, CD19-positive pre-pre-B-cell leukemias and hybrid leukemias (mixed myeloid and B-cell type) were consistently positive for CD72 on the cell surface. Therefore, CD72 may become an important marker for progenitor B-cell leukemias. PMID:1384316

Schwarting, R; Castello, R; Moldenhauer, G; Pezzutto, A; von Hoegen, I; Ludwig, W D; Parnes, J R; Dörken, B

1992-11-01

45

Leukemia among participants in military maneuvers at a nuclear bomb test  

SciTech Connect

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 myelocytic leukemia, one of hairy cell lymphocyctic leukemia, and one of acute lymphocytic luekemia. These findings represent a significant increase over the expected leukemia incidence of 3.5 cases. Mean film-badge gamma radiation dose for the study group was 466.2 mrem. (17 references, 3 tables)

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

1980-10-03

46

Occupational exposures, animal exposure and smoking as risk factors for hairy cell leukaemia evaluated in a case-control study  

Microsoft Academic Search

To evaluate occupational exposures as risk factors for hairy cell leukaemia (HCL), a population-based case-control study on 121 male HCL patients and 484 controls matched for age and sex was conducted. Elevated odds ratio (OR) was found for exposure to farm animals in general: OR 2.0, 95% confidence interval (CI) 1.2-3.2. The ORs were elevated for exposure to cattle, horse,

M Nordström; L Hardell; A Magnuson; H Hagberg; A Rask-Andersen

1998-01-01

47

A 72-kD B cell-associated surface glycoprotein expressed at high levels in hairy cell leukaemia and plasma cell neoplasms.  

PubMed Central

The present paper describes two new MoAbs, GHI/75 and VMP55, which were raised against a glycoprotein enriched lysate of hairy cell leukaemia. These antibodies recognized a new antigen of 72 kD (unreduced) and 83 kD (reduced) molecular weight. GHI/75 and VMP55 gave very strong staining of plasma cells, moderate labelling of circulating B cells but only weak staining of monocytes, some tissue macrophages and lymphoid cells. Neither antibody reacted with neutrophils or any non-haematopoietic cells. Both antibodies, however, strongly labelled the tumour cells in hairy cell leukaemia, multiple myeloma, plasmacytoma and lymphoplasmacytic lymphomas. No staining was seen of the neoplastic cells in Hodgkin's disease, myeloid leukaemia or T cell lymphomas. The two antibodies, GHI/75 and VMP55, may be of value in the differential diagnosis of hairy cell leukaemias and plasma cell neoplasms. In addition, the ease with which their antigen can be purified provides the possibility for a detailed study of this molecule. Images Fig. 1 Fig. 3

Pulford, K; Micklem, K; Thomas, J; Jones, M; Mason, D Y

1991-01-01

48

Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS  

ClinicalTrials.gov

Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

2011-12-09

49

Autologous and Allogeneic Typing of Human Leukemia Cells: Definition of Surface Antigens Restricted to Lymphocytic Leukemia Cells  

Microsoft Academic Search

Serum from a patient (CO) with acute lymphoblastic leukemia was reactive in immunoadherence assays with autologous leukemia cells but not with autologous blood lymphocytes or bone marrow cells during complete remission. Extensive absorption tests with an array of leukemia cells and normal cells were performed in order to define the specificity of the reaction. The autologous leukemia reactivity was either

Kazuyuki Naito; Hiroshi Yamaguchi; Keizo Horibe; Hiroshi Shiku; Toshitada Takahashi; Sakae Suzuki; Kazumasa Yamada

1983-01-01

50

711. Treatment of Acute Myeloid Leukemia by rAAV 8 Vector Mediated Human Interferon-? Gene Transfer  

Microsoft Academic Search

Alpha-interferons are widely used in the treatment of hematological malignancies such as CML, multiple myeloma and hairy cell leukemia. However their efficacy in the management of acute myeloid leukemia (AML) has not been fully evaluated. Furthermore the antitumour effects of the related ?-interferon have also not been systematically investigated in AML. Treatment with recombinant interferon is limited by its short

Reuben Benjamin; Andrew M. Davidoff; Pizzey Arnold; Nalini Singh; Asim Khwaja; Jenny McIntosh; Cathy C. Y. Ng; Tony Meager; Meenu Wadhwa; Amit C. Nathwani

2005-01-01

51

Hairy strings  

SciTech Connect

Zero modes of the world-sheet spinors of a closed string can source higher order moments of the bulk supergravity fields. In this work, we analyze various configurations of closed strings focusing on the imprints of the quantized spinor vacuum expectation values onto the tails of bulk fields. We identify supersymmetric arrangements for which all multipole charges vanish; while for others, we find that one is left with Neveu-Schwarz-Neveu-Schwarz, and Ramond-Ramond dipole and quadrupole moments. Our analysis is exhaustive with respect to all the bosonic fields of the bulk and to all higher order moments. We comment on the relevance of these results to entropy computations of hairy black holes of a single charge or more, and to open/closed string duality.

Sahakian, Vatche [Keck Laboratory, Harvey Mudd College, Claremont, California 91711 (United States)

2006-01-15

52

Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias  

Microsoft Academic Search

We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia

Ying Yan; Eric A Wieman; Xiuqin Guan; Ann A Jakubowski; Peter G Steinherz; Richard J O'Reilly

2009-01-01

53

Dynamic transcriptomes of human myeloid leukemia cells.  

PubMed

To identify the mechanisms controlling chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) in humans, we analyzed genome-wide transcription dynamics in three myeloid leukemia cell lines (K562, HL-60, and THP1) using high-throughput sequencing technology. Using KEGG analysis, we found that the ERK/MAPK, JAK-STAT and ErbB pathways promoted proliferation and metabolism in CML. However, in AML, differentiation and apoptosis blocking resulted in the accumulation of blast cells in marrow. In addition, each cell type had unique characteristics. K562 cells are an ideal model for studying erythroid differentiation and globin gene expression. The chemokine signaling pathway and Fc gamma R-mediated phagocytosis were markedly upregulated in HL-60 cells. In THP1 cells, highly expressed genes ensured strong phagocytosis by monocytes. Further, we provide a new insight into myeloid development. The abundant data sets and well-defined analysis methods will provide a resource and strategy for further investigation of myeloid leukemia. PMID:23806289

Wang, Hai; Hu, Haiyan; Zhang, Qian; Yang, Yadong; Li, Yanming; Hu, Yang; Ruan, Xiuyan; Yang, Yaran; Zhang, Zhaojun; Shu, Chang; Yan, Jiangwei; Wakeland, Edward K; Li, Quanzhen; Hu, Songnian; Fang, Xiangdong

2013-06-24

54

Musashi1 and Hairy and Enhancer of Split 1 High Expression Cells Derived from Embryonic Stem Cells Enhance the Repair of Small-Intestinal Injury in the Mouse  

Microsoft Academic Search

Background  Embryonic stem cells have great plasticity. In this study, we repaired impaired small intestine by transplanting putative\\u000a intestinal epithelial stem cells (Musashi1 and hairy and enhancer of split 1 high expression cells) derived from embryonic\\u000a stem cells.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The differentiation of definitive endoderm in embryoid bodies, derived from male ES-E14TG2a cells by the hanging-drop method,\\u000a was monitored to define a time

Tao YuShao-Yang; Shao-Yang Lan; Bin Wu; Qiu-Hui Pan; Liu Shi; Kai-Hong Huang; Ying Lin; Qi-Kui Chen

2011-01-01

55

Intermediate-sized filaments in leukemia cells.  

PubMed

Electron microscopic studies on human acute leukemias have shown that leukemic populations contain spherical and polarized cells in various proportions. As recorded by time-lapse cinematography, the two cell configurations represent different functional states: resting cells are completely spherical, locomotive cells are polarized with a conspicuous extension posteriorly. In 9 out of 12 cases of acute myeloid leukemia the two cell configurations were found to coincide with a different pattern of intermediate-sized filaments (ISF). Most spherical myeloblasts possessed large bundles of ISF (a minority had small bundles), whereas polarized myeloblasts showed small groups or single filaments. A similar correlation between cell shape and arrangement of ISF was observed in a transplantable undifferentiated rat leukemia. Two concepts can be distinguished with regard to the role of fibrillar structures in leukemic myeloblasts: thick bundles of ISF either represent a pathological state or have a functional significance. A tentative interpretation of our own results provides some arguments in favor of a disaggregation-reaggregation cycle of thick ISF bundles, whereas a pathological ("end stage") nature of these structures appears less likely. PMID:97858

Felix, H; Sträuli, P

1978-07-14

56

Exudation: an expanding technique for continuous production and release of secondary metabolites from plant cell suspension and hairy root cultures.  

PubMed

This review addresses methods of obtaining secondary metabolites from plant cell suspension and hairy root cultures and their exudates, particularly the physiological mechanisms of secondary metabolites release and trafficking. The efficiency for product recovery of metabolites can be increased by various methods, based on the principle of continuous product release into the cultivation medium. The most common methods for metabolite recovery are elicitation, influencing membrane permeability, and in situ product removal. The biosynthetic pathways can be influenced by cultivation conditions, transformation, or application of elicitors. The membrane permeability can be altered through the application of chemical or physical treatments. Product removal can be greatly increased through a two-phase system and the introduction of absorbents into the cultivation medium. In this review, we describe some improved approaches that have proven useful in these efforts. PMID:21987121

Cai, Zhenzhen; Kastell, Anja; Knorr, Dietrich; Smetanska, Iryna

2011-10-11

57

Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy  

Microsoft Academic Search

The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and\\/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them

A S M Yong; K Keyvanfar; R Eniafe; B N Savani; K Rezvani; E M Sloand; J M Goldman; A J Barrett; ASM Yong

2008-01-01

58

Methylation of gene CHFR promoter in acute leukemia cells  

Microsoft Academic Search

Summary  In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined\\u000a before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR. The\\u000a methylation of promoter in Molt-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR.

Gong Hui; Liu Wengli; Zhou Jianfeng; Xu Huizhen

2005-01-01

59

NOTCH1-induced T-cell leukemia in transgenic zebrafish  

Microsoft Academic Search

Activating mutations in the NOTCH1 gene have been found in about 60% of patients with T-cell acute lymphoblastic leukemia (T-ALL). In order to study the molecular mechanisms by which altered Notch signaling induces leukemia, a zebrafish model of human NOTCH1-induced T-cell leukemia was generated. Seven of sixteen mosaic fish developed a T-cell lymphoproliferative disease at about 5 months. These neoplastic

J Chen; C Jette; J P Kanki; J C Aster; A T Look; J D Griffin

2007-01-01

60

Adult T-Cell Leukemia\\/Lymphoma not Associated with Human T-Cell Leukemia Virus Type I  

Microsoft Academic Search

We describe five patients with adult T-cell leukemia\\/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those

Masanori Shimoyama; Yoshitoyo Kagami; Kunitada Shimotohno; Masanao Miwa; Keisuke Minato; Kensei Tobinai; Keiichi Suemasu; Takashi Sugimura

1986-01-01

61

Cell cycle control in acute myeloid leukemia  

PubMed Central

Acute myeloid leukemia (AML) is the result of a multistep transforming process of hematopoietic precursor cells (HPCs) which enables them to proceed through limitless numbers of cell cycles and to become resistant to cell death. Increased proliferation renders these cells vulnerable to acquiring mutations and may favor leukemic transformation. Here, we review how deregulated cell cycle control contributes to increased proliferation in AML and favors genomic instability, a prerequisite to confer selective advantages to particular clones in order to adapt and independently proliferate in the presence of a changing microenvironment. We discuss the connection between differentiation and proliferation with regard to leukemogenesis and outline the impact of specific alterations on response to therapy. Finally, we present examples, how a better understanding of cell cycle regulation and deregulation has already led to new promising therapeutic strategies.

Schnerch, Dominik; Yalcintepe, Jasmin; Schmidts, Andrea; Becker, Heiko; Follo, Marie; Engelhardt, Monika; Wasch, Ralph

2012-01-01

62

An interchangeable system of hairy root and cell suspension cultures of Catharanthus roseus for indole alkaloid production  

Microsoft Academic Search

Hairy roots ofCatharanthus roseus obtained by co-cultivation of hypocotyl segments withAgrobacterium rhizogenes, and cultured in SH (Schenk and Hildebrandt) basal medium, formed two types of calli when subcultured in SH medium with 1 mg\\/1 a-naphthaleneacetic acid and 0.1 mg\\/l kinetin. One of them, a compact callus, when re-subcultured in SH basal medium gave rise to hairy roots again. A rhizogenic

Kyung Hee Jung; Sang Soo Kwak; Cha Yong Choi; Jang R. Liu

1995-01-01

63

Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism  

PubMed Central

In acute myeloid leukemia (AML), the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs) in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML.

Pezeshkian, Bahareh; Donnelly, Christopher; Tamburo, Kelley; Geddes, Timothy; Madlambayan, Gerard J.

2013-01-01

64

Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism.  

PubMed

In acute myeloid leukemia (AML), the chances of achieving disease-free survival are low. Studies have demonstrated a supportive role of endothelial cells (ECs) in normal hematopoiesis. Here we show that similar intercellular relationships exist in leukemia. We demonstrate that leukemia cells themselves initiate these interactions by directly modulating the behavior of resting ECs through the induction of EC activation. In this inflammatory state, activated ECs induce the adhesion of a sub-set of leukemia cells through the cell adhesion molecule E-selectin. These adherent leukemia cells are sequestered in a quiescent state and are unaffected by chemotherapy. The ability of adherent cells to later detach and again become proliferative following exposure to chemotherapy suggests a role of this process in relapse. Interestingly, differing leukemia subtypes modulate this process to varying degrees, which may explain the varied response of AML patients to chemotherapy and relapse rates. Finally, because leukemia cells themselves induce EC activation, we postulate a positive-feedback loop in leukemia that exists to support the growth and relapse of the disease. Together, the data defines a new mechanism describing how ECs and leukemia cells interact during leukemogenesis, which could be used to develop novel treatments for those with AML. PMID:23560111

Pezeshkian, Bahareh; Donnelly, Christopher; Tamburo, Kelley; Geddes, Timothy; Madlambayan, Gerard J

2013-04-01

65

RNA viral vectors for improved Agrobacterium-mediated transient expression of heterologous proteins in Nicotiana benthamiana cell suspensions and hairy roots  

PubMed Central

Background Plant cell suspensions and hairy root cultures represent scalable protein expression platforms. Low protein product titers have thus far limited the application of transient protein expression in these hosts. The objective of this work was to overcome this limitation by harnessing A. tumefaciens to deliver replicating and non-replicating RNA viral vectors in plant tissue co-cultures. Results Replicating vectors derived from Potato virus X (PVX) and Tobacco rattle virus (TRV) were modified to contain the reporter gene ?-glucuronidase (GUS) with a plant intron to prevent bacterial expression. In cell suspensions, a minimal PVX vector retaining only the viral RNA polymerase gene yielded 6.6-fold more GUS than an analogous full-length PVX vector. Transient co-expression of the minimal PVX vector with P19 of Tomato bushy stunt virus or HC-Pro of Tobacco etch virus to suppress post-transcriptional gene silencing increased GUS expression by 44 and 83%, respectively. A non-replicating vector containing a leader sequence from Cowpea mosaic virus (CPMV-HT) modified for enhanced translation led to 70% higher transient GUS expression than a control treatment. In hairy roots, a TRV vector capable of systemic movement increased GUS accumulation by 150-fold relative to the analogous PVX vector. Histochemical staining for GUS in TRV-infected hairy roots revealed the capacity for achieving even higher productivity per unit biomass. Conclusions For the first time, replicating PVX vectors and a non-replicating CPMV-HT vector were successfully applied toward transient heterologous protein expression in cell suspensions. A replicating TRV vector achieved transient GUS expression levels in hairy roots more than an order of magnitude higher than the highest level previously reported with a viral vector delivered by A. tumefaciens.

2012-01-01

66

75 FR 53202 - Diseases Associated With Exposure to Certain Herbicide Agents (Hairy Cell Leukemia and Other...  

Federal Register 2010, 2011, 2012, 2013

...effective dates for benefits earlier than the date the final regulation...from conducting additional research and studies regarding Parkinson's...be created to define needed research and studies on diseases and...there is a relationship between PTSD or stress and...

2010-08-31

67

Characterization of chronic myeloid leukemia stem cells  

PubMed Central

Though tyrosine kinase inhibitors have redefined the care of chronic myeloid leukemia (CML), these agents have not proved curative, likely due to resistance of the leukemia stem cells (LSC). While a number of potential therapeutic targets have emerged in CML, their expression in the LSC remains largely unknown. We therefore isolated subsets of CD34+ stem/progenitor cells from normal donors and from patients with chronic phase or blast crisis CML. These cell subsets were then characterized based on ability to engraft immunodeficient mice and expression of candidate therapeutic targets. The CD34+CD38? CML cell population with high aldehyde dehydrogenase (ALDH) activity was the most enriched for immunodeficient mouse engrafting capacity. The putative targets: PROTEINASE 3, SURVIVIN, and hTERT were expressed only at relatively low levels by the CD34+CD38?ALDHhigh CML cells, similar to the normal CD34+CD38?ALDHhigh cells and less than in the total CML CD34+ cells. In fact, the highest expression of these antigens was in normal, unfractionated CD34+ cells. In contrast, PRAME and WT1 were more highly expressed by all CML CD34+ subsets than their normal counterparts. Thus, ALDH activity appears to enrich for CML stem cells, which display an expression profile that is distinct from normal stem/progenitor cells and even the CML progenitors. Indeed, expression of a putative target by the total CD34+ population in CML does not guarantee expression by the LSC. These expression patterns suggest that PROTEINASE 3, SURVIVIN, and hTERT are not optimal therapeutic targets in CML stem cells; whereas PRAME and WT1 seem promising.

Gerber, Jonathan M.; Qin, Lu; Kowalski, Jeanne; Smith, B. Douglas; Griffin, Constance A.; Vala, Milada S.; Collector, Michael I.; Perkins, Brandy; Zahurak, Marianna; Matsui, William; Gocke, Christopher D.; Sharkis, Saul J.; Levitsky, Hyam I.; Jones, Richard J.

2010-01-01

68

In vitro activity of vinorelbine on human leukemia cells.  

PubMed

Vinorelbine (VNR) is a semi-synthetic Vinca rosea alkaloid that has been employed both as a single agent and in combination, and has shown significant antitumor activity. As little is known about VNR activity on human leukemia, we studied its in vitro cytotoxic effect on human leukemia cell lines (FLG 29.1, HL60, K562, Balm 4, CEM and Daudi) and on fresh leukemia cells from 28 patients: 2 acute myeloid leukemia (AML); 3 chronic myeloid leukemia in blastic phase (CML-BP); 5 acute lymphoblastic leukemia (ALL); 18 B-chronic lymphatic leukemia (B-CLL), employing the colorimetric INT assay and determining the IC50. We observed that VNR exerts its cytotoxic activity on leukemic cell lines in a dose-dependent fashion. The lymphoid cell lines appear more sensitive than the myeloid ones to the VNR-dependent growth inhibition. A similar pattern was noticed for leukemia cells in primary cultures. VNR is not effective on CML-BP cells, shows variable activity on the AML and ALL cells and is very effective against B-CLL cells. VNR inhibited the growth of fresh B-CLL cells from 15 of 18 patients, the IC50 doses ranging from 4 ng/ml to 83 microg/ml (doses coinciding with the plasma levels obtained in clinics). These observations strongly suggest that VNR could be useful in clinics for the treatment of B-CLL. PMID:11450890

Landini, I; Bartolozzi, B; Banchelli, I; Degli Innocenti, A; Nocentini, O; Bernabei, P A

2001-06-01

69

Stem cell leukemia protein directs hematopoietic stem cell fate  

Microsoft Academic Search

Stem cell leukemia (SCL) protein has been shown to be an essential transcription factor during hematopoietic development in the embryo. In adult hematopoiesis, however, the role for SCL has remained largely unknown, whereas it is expressed in bone marrow hematopoietic stem cells (HSCs). In this study, we performed HSC transplantation and an in vitro HSC differen- tiation assay using retrovirally

Atsushi Kunisato; Shigeru Chiba; Toshiki Saito; Keiki Kumano; Etsuko Nakagami-Yamaguchi; Tomoyuki Yamaguchi; Hisamaru Hirai

2004-01-01

70

How I treat plasma cell leukemia.  

PubMed

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum ?(2)-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine receptors. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. In this review, we provide an overview of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients. PMID:22837533

van de Donk, Niels W C J; Lokhorst, Henk M; Anderson, Kenneth C; Richardson, Paul G

2012-07-26

71

Analyzing the effect of decreasing cytosolic triosephosphate isomerase on Solanum tuberosum hairy root cells using a kinetic-metabolic model.  

PubMed

A kinetic-metabolic model of Solanum tuberosum hairy roots is presented in the interest of understanding the effect on the plant cell metabolism of a 90% decrease in cytosolic triosephosphate isomerase (cTPI, EC 5.3.1.1) expression by antisense RNA. The model considers major metabolic pathways including glycolysis, pentose phosphate pathway, and TCA cycle, as well as anabolic reactions leading to lipids, nucleic acids, amino acids, and structural hexoses synthesis. Measurements were taken from shake flask cultures for six extracellular nutrients (sucrose, fructose, glucose, ammonia, nitrate, and inorganic phosphate) and 15 intracellular compounds including sugar phosphates (G6P, F6P, R5P, E4P) and organic acids (PYR, aKG, SUCC, FUM, MAL) and the six nutrients. From model simulations and experimental data it can be noted that plant cell metabolism redistributes metabolic fluxes to compensate for the cTPI decrease, leading to modifications in metabolites levels. Antisense roots showed increased exchanges between the pentose phosphate pathway and the glycolysis, an increased oxygen uptake and growth rate. PMID:23055265

Valancin, Alexandre; Srinivasan, Balasubrahmanyan; Rivoal, Jean; Jolicoeur, Mario

2012-10-18

72

Discovery of adult T-cell leukemia  

PubMed Central

Adult T-cell leukemia (ATL) was first reported as a distinct clinical entity in 1977 in Japan. The predominant physical findings are skin lesions, lymphadenopathy and hepatosplenomegaly. The ATL cells are of mature T-helper phenotype and have a characteristic appearance with indented nuclei. There is striking frequent hypercalcemia with increased numbers of osteoclasts. Central to the identification of the disease is a striking geographic clustering in southwestern Japan and the isolation of human T-cell lymphotropic virus type-1 (HTLV-1) from the cell lines of patients. Worldwide epidemiological studies have been made through international collaborations. Several diseases were found to be related to HTLV-1 infection. Moreover, it was noted that an immunodeficiency state may be induced by HTLV-1 infection. In Japan, HTLV-1 carriers have been estimated to be 1.2 million, and more than 700 cases of ATL have been diagnosed each year.

Takatsuki, Kiyoshi

2005-01-01

73

Cordycepin Regulates GSK-3?/?-Catenin Signaling in Human Leukemia Cells  

PubMed Central

Background Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/?-catenin pathway is required for the survival and development of LSCs. Therefore, targeting ?-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates ?-catenin expression in leukemia cells. Methodology and Principal Findings In this study, we found that cordycepin significantly suppressed cell proliferation in all malignant cancer cells, including U937, K562, A549, HepG2, SK-Hep1 and MCF7 in a dose-dependent manner. However, cordycepin reduced ?-catenin levels in U937, K562 and THP1 leukemia cells and had no effect on other solid cancer cells. In addition, treatment with cordycepin significantly suppressed leukemia colony formation in soft agar assay. Cordycepin enhanced proteasome-dependent degradation and inhibited nuclear translocation of ?-catenin in leukemia cells. Cordycepin-reduced ?-catenin stability was restored by the addition of a pharmacological inhibitor of GSK-3?, indicating that cordycepin-suppressed ?-catenin stability is mediated by the activation of GSK-3?. Furthermore, cordycepin abolished the effect of Wnt3a-induced ?-catenin in leukemia cells. In addition, cordycepin-impaired ?-catenin is regulated by Akt activation but is not significantly influenced by AMPK or mTOR signal pathways. Significance Our findings show for the first time that codycepin selectively reduces ?-catenin stability in leukemia but not in other solid tumor cells. This suppressive effect is mediated by regulating GSK-3?. A synergistic combination of cordycepin with other treatments should be used as a novel strategy to eradicate leukemia via elimination of LSCs.

Liu, Tzu-An; Tzean, Shean-Shong; Shen, Tang-Long; Liou, Jun-Yang

2013-01-01

74

Lysis of leukemia cells by spleen cells of normal mice.  

PubMed Central

Spleen cells from 2- to 3-month-old normal mice of some strains having a low incidence of spontaneous leukemia were found to lyse cells of the spontaneous AKR leukemia K36 in the 51Cr release assay. Incubation of 51Cr-labeled ADR K36 cells with spleen cells from normal C57BL/6, C57L, C57BL/10, and RF mice resulted in the release of significantly more 51Cr than that released in the presence of medium alone. In contrast, 51Cr released from AKR K36 cells after incubation with spleen cells from mice of the high leukemic strains AKR and C58 was less than that released spontaneously. The results of competitive inhibition tests when C57BL/6 spleen cells were incubated simultaneously with 51Cr-labeled AKR K36 target cells and varying numbers of nonlabeled cells demonstrated that the cytotoxic activity of normal C57BL/6 spleen cells was directed against an antigen(s) associated with several leukemias, but that was undetectable on normal thymocytes. Pretreatment of C57BL/6 spleen cells with carbonyl iron and a magnet, which removed phagocytic macrophages, did not decrease the cytotoxic acitivity for AKR K36 cells.

Zarling, J M; Nowinski, R C; Bach, F H

1975-01-01

75

Isolation of immortal cell lines from the first stage of murine leukemia virus-induced leukemia.  

PubMed

Friend murine leukemia virus (F-MuLV) is a replication-competent retrovirus that induces a rapidly fetal leukemia in susceptible mice (stage I disease). Leukemia cells obtained from these animals do not grow in cell culture using standard tissue culture conditions. However, in the presence of WEHI-3 cell-conditioned medium (CM), 100% of spleen or bone marrow explants from diseased mice yield immortal cell lines. These cell lines exhibit the same growth properties, produce the same viruses, and express the same oncogenes as the leukemia cells found in mice with stage I disease. No cell lines were obtained from leukemic mice in the absence of CM. No cell lines were obtained from uninfected adult, newborn, or phenylhydrazine-treated animals with or without CM. We conclude that some of the hematopoietic cells in F-MuLV-diseased mice will proliferate indefinitely in the presence of CM. The development of this abnormal response to CM is one of the early changes associated with F-MuLV-induced leukemia. PMID:6591200

Oliff, A; Oliff, I; Schmidt, B; Famulari, N

1984-09-01

76

Isolation of immortal cell lines from the first stage of murine leukemia virus-induced leukemia.  

PubMed Central

Friend murine leukemia virus (F-MuLV) is a replication-competent retrovirus that induces a rapidly fetal leukemia in susceptible mice (stage I disease). Leukemia cells obtained from these animals do not grow in cell culture using standard tissue culture conditions. However, in the presence of WEHI-3 cell-conditioned medium (CM), 100% of spleen or bone marrow explants from diseased mice yield immortal cell lines. These cell lines exhibit the same growth properties, produce the same viruses, and express the same oncogenes as the leukemia cells found in mice with stage I disease. No cell lines were obtained from leukemic mice in the absence of CM. No cell lines were obtained from uninfected adult, newborn, or phenylhydrazine-treated animals with or without CM. We conclude that some of the hematopoietic cells in F-MuLV-diseased mice will proliferate indefinitely in the presence of CM. The development of this abnormal response to CM is one of the early changes associated with F-MuLV-induced leukemia. Images

Oliff, A; Oliff, I; Schmidt, B; Famulari, N

1984-01-01

77

Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory 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

2013-05-01

78

Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma  

ClinicalTrials.gov

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

2013-07-01

79

Dendritic cell vaccination in acute myeloid leukemia.  

PubMed

The prognosis of patients with acute myeloid leukemia (AML) remains dismal, with a 5-year overall survival rate of only 5.2% for the continuously growing subgroup of AML patients older than 65 years. These patients are generally not considered eligible for intensive chemotherapy and/or allogeneic hematopoietic stem cell transplantation because of high treatment-related morbidity and mortality, emphasizing the need for novel, less toxic, treatment alternatives. It is within this context that immunotherapy has gained attention in recent years. In this review, we focus on the use of dendritic cell (DC) vaccines for immunotherapy of AML. DC are central orchestrators of the immune system, bridging innate and adaptive immunity and critical to the induction of anti-leukemic immunity. We discuss the rationale and basic principles of DC-based therapy for AML and review the clinical experience that has been obtained so far with this form of immunotherapy for patients with AML. PMID:22686130

Anguille, Sébastien; Willemen, Yannick; Lion, Eva; Smits, Evelien L; Berneman, Zwi N

2012-07-01

80

A hybrid form of myeloid/NK-cell acute leukemia and myeloid/NK-cell precursor acute leukemia.  

PubMed

Natural killer (NK)-cell leukemia/lymphoma is a rare entity that has been defined only in recent years. In the Revised European-American Lymphoma and World Health Organization classifications, only the mature NK-cell malignancies are included. However, at least 3 types of precursor NK-cell neoplasms have been reported in the literature. These include myeloid/NK-cell acute leukemia, myeloid/NK-cell precursor acute leukemia, and blastic NK-cell lymphoma/leukemia. These leukemias are characterized by the presence of blasts, which express CD56, in the peripheral blood, bone marrow, lymph nodes, and/or extranodal tissues. We report a case that is morphologically consistent with myeloid/NK-cell acute leukemia but immunologically is myeloid/NK-cell precursor acute leukemia. This case is unique in its cutaneous presentation without involvement of the peripheral blood. Extensive flow cytometric studies were performed on the skin biopsy and bone marrow aspirate specimens, which included many markers that had not been tested before in these entities. The clinical implications of these findings are discussed. PMID:12792926

Sun, Tsieh; Pashaei, Shayesteh; Jaffrey, Ira; Ryder, John

2003-05-01

81

Immunophenotypic characterization of T-cell prolymphocytic leukemia.  

PubMed

Objectives: To review clinical data, cytogenetic findings, and flow cytometric analysis in 20 patients with T-cell prolymphocytic leukemia (T-PLL), a rare, aggressive, mature T-cell leukemia with poor prognosis and short survival. Methods: Using multiparameter flow cytometry with a large combination of antibodies, we summarize the immunophenotypic features of T-PLL, including unusual immunophenotypic variants, and illustrate immunophenotypic clues that may help distinguish this entity from other T-cell malignancies. Results: By flow cytometry, T-PLL is characterized by a postthymic mature T-cell immunophenotype with a variety of abnormalities that usually allow distinction from other mature T-cell leukemias. Conclusions: Although definitive diagnosis of T-PLL requires a systemic approach with integration of clinical data, morphology, immunophenotype, cytogenetics/fluorescence in situ hybridization, and molecular features, our results indicate immunophenotyping by multiparameter flow cytometry greatly facilitates diagnosis and assists with subclassification of this mature T-cell leukemia. PMID:24124154

Chen, Xueyan; Cherian, Sindhu

2013-11-01

82

Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed By Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma  

ClinicalTrials.gov

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; 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 Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

2013-05-06

83

Cell Trafficking in Chronic Lymphocytic Leukemia.  

PubMed

Chronic lymphocytic leukemia (CLL) is an indolent lymphoproliferative disorder characterized by both circulating peripheral disease as well as involvement of the lymph nodes and bone marrow. Increasing evidence suggests that the stromal microenvironment provides anti-apoptotic and pro-survival signals to CLL cells, and may contribute significantly to resistance to a wide variety of treatments. Our understanding of the complex interactions involved in CLL cell trafficking continues to grow. Chemokines and corresponding chemokine receptors are key factors for organizing CLL cell trafficking and homing and the complex cellular interactions between CLL and accessory cells. Important chemokines include CCL3, CCL4, and CCL22, which are released by CLL cells, and CXCL12, CXCL13, CXCL9, 10, 11, CCL 19, and CCL21, which are constitutively secreted by various stromal cells. Integrins such as VLA-4 (CD49d) as well as selectins and CD44 also likely play a role in directing CLL cell migration within the tissue microenvironments. Data are also emerging that other molecules such as MMP-9 and cytoskeletal proteins also contribute to CLL cell trafficking. Though this interplay is complex, it is critical that we improve our understanding of CLL cell trafficking to facilitate the development of novel therapies that target these pathways. Several drugs in clinical development, such as CXCR4 antagonists and PI3K, Btk, and Syk inhibitors appear to modulate CLL cell trafficking and CLL-stroma interactions. Here, we review the current understanding of the molecular interactions that underlie CLL cell trafficking and we highlight some of the promising approaches underway to target these pathways therapeutically in CLL. PMID:22844583

Davids, Matthew S; Burger, Jan A

2012-02-21

84

Targeting Myelogenous Leukemia Stem Cells: Role of the Circulation  

PubMed Central

Unlike stem cells from solid tumors, the stem cells which initiate myelogenous leukemias arise in marrow, an organ with a unique circulation which allows ready access of leukemia cells, including leukemia stem cells (LSCs), to the vasculature. This poses unique problems in the targeting of LSCs since these cells are found circulating in the majority of leukemia cases at diagnosis and are usually not detectable during remission states. Because most cases of leukemia relapse, it is suggested that LSCs remain quiescent in the marrow until they eventually proliferate and circulate again. This indicates that effective targeting of LSCs must occur not only in peripheral circulation but in the micro-circulation of the marrow. Targeting such interactions may overcome cell adhesion-mediated treatment resistance, other multi-drug resistance mechanisms, and opportunities for clonal evolution in the marrow environment. Targeting selectins and integrins, signal transduction mediators, and chemokine/cytokine networks in the marrow micro-circulation may aid in abrogating leukemia-initiating stem cells which contribute to disease relapse. LSCs possess surface antigen profiles and signal transduction activation profiles which may allow differential targeting as compared with normal hematopoietic stem cells.

Liesveld, Jane

2012-01-01

85

Hairy transcriptional repression targets and cofactor recruitment in Drosophila.  

PubMed

Members of the widely conserved Hairy/Enhancer of split family of basic Helix-Loop-Helix repressors are essential for proper Drosophila and vertebrate development and are misregulated in many cancers. While a major step forward in understanding the molecular mechanism(s) surrounding Hairy-mediated repression was made with the identification of Groucho, Drosophila C-terminal binding protein (dCtBP), and Drosophila silent information regulator 2 (dSir2) as Hairy transcriptional cofactors, the identity of Hairy target genes and the rules governing cofactor recruitment are relatively unknown. We have used the chromatin profiling method DamID to perform a global and systematic search for direct transcriptional targets for Drosophila Hairy and the genomic recruitment sites for three of its cofactors: Groucho, dCtBP, and dSir2. Each of the proteins was tethered to Escherichia coli DNA adenine methyltransferase, permitting methylation proximal to in vivo binding sites in both Drosophila Kc cells and early embryos. This approach identified 40 novel genomic targets for Hairy in Kc cells, as well as 155 loci recruiting Groucho, 107 loci recruiting dSir2, and wide genomic binding of dCtBP to 496 loci. We also adapted DamID profiling such that we could use tightly gated collections of embryos (2-6 h) and found 20 Hairy targets related to early embryogenesis. As expected of direct targets, all of the putative Hairy target genes tested show Hairy-dependent expression and have conserved consensus C-box-containing sequences that are directly bound by Hairy in vitro. The distribution of Hairy targets in both the Kc cell and embryo DamID experiments corresponds to Hairy binding sites in vivo on polytene chromosomes. Similarly, the distributions of loci recruiting each of Hairy's cofactors are detected as cofactor binding sites in vivo on polytene chromosomes. We have identified 59 putative transcriptional targets of Hairy. In addition to finding putative targets for Hairy in segmentation, we find groups of targets suggesting roles for Hairy in cell cycle, cell growth, and morphogenesis, processes that must be coordinately regulated with pattern formation. Examining the recruitment of Hairy's three characterized cofactors to their putative target genes revealed that cofactor recruitment is context-dependent. While Groucho is frequently considered to be the primary Hairy cofactor, we find here that it is associated with only a minority of Hairy targets. The majority of Hairy targets are associated with the presence of a combination of dCtBP and dSir2. Thus, the DamID chromatin profiling technique provides a systematic means of identifying transcriptional target genes and of obtaining a global view of cofactor recruitment requirements during development. PMID:15252443

Bianchi-Frias, Daniella; Orian, Amir; Delrow, Jeffrey J; Vazquez, Julio; Rosales-Nieves, Alicia E; Parkhurst, Susan M

2004-07-13

86

Hairy Transcriptional Repression Targets and Cofactor Recruitment in Drosophila  

PubMed Central

Members of the widely conserved Hairy/Enhancer of split family of basic Helix-Loop-Helix repressors are essential for proper Drosophila and vertebrate development and are misregulated in many cancers. While a major step forward in understanding the molecular mechanism(s) surrounding Hairy-mediated repression was made with the identification of Groucho, Drosophila C-terminal binding protein (dCtBP), and Drosophila silent information regulator 2 (dSir2) as Hairy transcriptional cofactors, the identity of Hairy target genes and the rules governing cofactor recruitment are relatively unknown. We have used the chromatin profiling method DamID to perform a global and systematic search for direct transcriptional targets for Drosophila Hairy and the genomic recruitment sites for three of its cofactors: Groucho, dCtBP, and dSir2. Each of the proteins was tethered to Escherichia coli DNA adenine methyltransferase, permitting methylation proximal to in vivo binding sites in both Drosophila Kc cells and early embryos. This approach identified 40 novel genomic targets for Hairy in Kc cells, as well as 155 loci recruiting Groucho, 107 loci recruiting dSir2, and wide genomic binding of dCtBP to 496 loci. We also adapted DamID profiling such that we could use tightly gated collections of embryos (2–6 h) and found 20 Hairy targets related to early embryogenesis. As expected of direct targets, all of the putative Hairy target genes tested show Hairy-dependent expression and have conserved consensus C-box–containing sequences that are directly bound by Hairy in vitro. The distribution of Hairy targets in both the Kc cell and embryo DamID experiments corresponds to Hairy binding sites in vivo on polytene chromosomes. Similarly, the distributions of loci recruiting each of Hairy's cofactors are detected as cofactor binding sites in vivo on polytene chromosomes. We have identified 59 putative transcriptional targets of Hairy. In addition to finding putative targets for Hairy in segmentation, we find groups of targets suggesting roles for Hairy in cell cycle, cell growth, and morphogenesis, processes that must be coordinately regulated with pattern formation. Examining the recruitment of Hairy's three characterized cofactors to their putative target genes revealed that cofactor recruitment is context-dependent. While Groucho is frequently considered to be the primary Hairy cofactor, we find here that it is associated with only a minority of Hairy targets. The majority of Hairy targets are associated with the presence of a combination of dCtBP and dSir2. Thus, the DamID chromatin profiling technique provides a systematic means of identifying transcriptional target genes and of obtaining a global view of cofactor recruitment requirements during development.

Bianchi-Frias, Daniella; Orian, Amir; Delrow, Jeffrey J; Vazquez, Julio; Rosales-Nieves, Alicia E

2004-01-01

87

Immunotherapy of acute myeloid leukemia based on ?? T cells  

PubMed Central

A current major challenge of acute myeloid leukemia research is to develop immunotherapeutic strategies that would be employable in all patients. We recently reported that appropriately stimulated ?? T cells are fully capable of mediating cytotoxicity against leukemic blasts.

Gertner-Dardenne, Julie; Fauriat, Cyril; Vey, Norbert; Olive, Daniel

2012-01-01

88

Laser nanothermolysis of human leukemia cells using functionalized plasmonic nanoparticles  

PubMed Central

In the present work, we present the use of gold nanorods as plasmonic nanoparticles for selective photothermal therapy of human acute (HL-60) and chronicle (K-562) leukemia cells using a near-infrared laser. We improved a published methodology of gold nanorods conjugation to generate high yields of narrow band gold nanorods with an optical absorption centered at 760 nm. The manufactured nanorods were pegylated and conjugated with monoclonal antibody to become non-toxic as biocompatible nanothermolysis agent. Gold nanorods are synthesized and conjugated to CD33 monoclonal antibody. After pegylation, or conjugation with CD33 antibody, gold nanorods were non-toxic to acute and chronic leukemia cells. Our modified gold nanorods CD33 conjugates shown high level of accumulation for both leukemia cell lines, and successful used for nanothermolysis of human leukemia cells in vitro. Each sample was illuminated with 1 or 3 laser shots as for low and for high laser fluence. The radiation was provided by a Quanta Systems q-switched titanium sapphire laser, and the system was designed for maximum sample coverage using non-focused illumination. HL-60 and K-562 cells were treated for 45 min with gold nanorods CD33 conjugated, or with pegylated gold nanorods. The effect of pulsed-laser nanothermolysis for acute and chronic leukemia cells were investigated with cell counting for number of living cells, percentage of cell death and functional parameters such as damage of cell membrane and metabolic activity. Gold nanorods CD33 conjugates significantly increase cell damage for low fluence laser and completely destroyed cancer cells after 3 pulses for low fluence (acute leukemia) and for high fluence laser as for HL-60 (acute) and for K-562 (chronicle) leukemia cells.

Liopo, Anton V.; Conjusteau, Andre; Konopleva, Marina; Andreeff, Michael; Oraevsky, Alexander A.

2012-01-01

89

The role of natural killer cells in chronic myeloid leukemia  

PubMed Central

Chronic myeloid leukemia is a neoplasia resulting from a translocation between chromosomes 9 and 22 producing the BCR-ABL hybrid known as the Philadelphia chromosome (Ph). In chronic myeloid leukemia a proliferation of malignant myeloid cells occurs in the bone marrow due to excessive tyrosine kinase activity. In order to maintain homeostasis, natural killer cells, by means of receptors, identify the major histocompatibility complex on the surface of tumor cells and subsequently induce apoptosis. The NKG2D receptor in the natural killer cells recognizes the transmembrane proteins related to major histocompatibility complex class I chain-related genes A and B (MICA and MICB), and it is by the interaction between NKG2D and MICA that natural killer cells exert cytotoxic activity against chronic myeloid leukemia tumor cells. However, in the case of chronic exposure of the NKG2D receptor, the MICA ligand releases soluble proteins called sMICA from the tumor cell surface, which negatively modulate NKG2D and enable the tumor cells to avoid lysis mediated by the natural killer cells. Blocking the formation of sMICA may be an important antitumor strategy. Treatment using tyrosine kinase inhibitors induces modulation of NKG2DL expression, which could favor the activity of the natural killer cells. However this mechanism has not been fully described in chronic myeloid leukemia. In the present study, we analyze the role of natural killer cells to reduce proliferation and in the cellular death of tumor cells in chronic myeloid leukemia.

Danier, Anna Carolyna Araujo; de Melo, Ricardo Pereira; Napimoga, Marcelo Henrique; Laguna-Abreu, Maria Theresa Ceravolo

2011-01-01

90

Stereologic analysis of the ultrastructure of isolated human T and non-T lymphoid cells  

Microsoft Academic Search

Summary  Malignant cells from 9 cases of chronic lymphocytic leukemia (CLL), 4 cases of prolymphocytic leukemia (PLL), 4 cases of hairy\\u000a cell leukemia (HCL), 4 cases of malignant lymphoma of centrocytic type and 3 cases of malignant lymphoma of lymphoblastic\\u000a type (Kiel classification), all examined for T and B markers, were analysed by electron microscopy. Stereological methods\\u000a were applied to assess

Anne Marie Boesen

1983-01-01

91

Leukemia  

MedlinePLUS

... leukemia /DS00351 ">Leukemia Guidelines for sites linking to MayoClinic.com Advertisement Mayo Clinic Store Check out these best-sellers and special offers on books and newsletters from Mayo Clinic. Try Mayo Clinic Health Letter ... answers to live stronger, longer and healthier at any age ...

92

B cell acute lymphoblastic leukemia (ALL) in donor cells following bone marrow transplantation for T cell ALL.  

PubMed

Leukemia recurred in a child with acute lymphoblastic leukemia after a bone marrow transplant. The pre-transplant leukemia was of T cell origin whereas the post-transplant relapse leukemia was of B cell origin. The recurrence was shown to be in donor cells by analysis of chromosomes and restriction fragment length polymorphisms. Although the mechanism of leukemia induction is uncertain, the possibilities of donor relapse due to EBV infection or chromosomal exchange were disproven. An alternative mechanism must account for leukemia induction in this patient. PMID:2844347

Feig, S A; Dreazen, O; Simon, M; Wiley, F; Schreck, R; Gale, R P

1988-07-01

93

Plant Cell and Hairy Root Cultures in Bioreactor-Based Production Processes.  

National Technical Information Service (NTIS)

Plant cell culture technology has progressed rapidly during recent decades to the point where a number of process systems have achieved or are approaching commercial operation. The aim of the work was to develop laboratory scale bietechnical production pr...

A. M. Nuutila

1994-01-01

94

Utilization of Catharanthus Roseus Hairy Root and Cell Suspension Cultures in Plant Biotechnology.  

National Technical Information Service (NTIS)

Plant cell culture technology finds increasing use in agricultural crop improvement, germplasm storage and commercial micropropagation as well as in fundamental studies of plant biochemistry, physiology and genetics. The production of useful chemicals by ...

L. Toivonen

1992-01-01

95

Acid alpha-naphthyl acetate esterase in hairy cell leukemia cells and other cells of the hematopoietic system  

Microsoft Academic Search

Zusammenfassung Das Vorkommen und das Reaktionsbild vona-Naphthyl-Acetat-Esterase bei pH 5,8 (saure Esterase) wurde in den Zellen von 10 Haarzell-Leukämien untersucht. Alle 10 Haarzell-Leukämie-Fälle — darunter zwei Fälle mit nur vereinzelten tartratresistenten saure Phosphatase-positiven Zellen — waren mäßig stark bis stark saure Esterase-positiv. Die saure Esterase-Aktivität war in feinen bis groben Granula meist semizirkulär um den Zellkern verteilt. Dieses Reaktionsbild fand

G. Tolksdorf; H. Stein

1979-01-01

96

Leukemia -- Chronic T-Cell Lymphocytic  

MedlinePLUS

... note these links take you to other sections: ASCO Answers Fact Sheet : Read a one-page fact ... Video : View a short video led by an ASCO expert in leukemia that provides basic information and ...

97

Detection and characterization of human high molecular weight B cell growth factor receptors on leukemic B cells in chronic lymphocytic leukemia.  

PubMed Central

Human high molecular weight-B cell growth factor (HMW-BCGF) (60 kD) stimulates activated normal B cells, B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, hairy cell leukemia (HCL) cells, prolymphocytic leukemia (PLL) cells, and chronic lymphocytic leukemia (CLL) cells. The expression of human high molecular weight B cell growth factor (HMW-BCGF) receptors (R) on clonal populations of leukemic B cells in CLL was studied by ligand binding assays using 125I-labeled HMW-BCGF as well as by immunofluorescence/flow cytometry and Scatchard analyses using an anti-HMW-BCGF R monoclonal antibody (MAb), designated BA-5. There was a high correlation between HMW-BCGF R expression and responsiveness to HMW-BCGF. 60% of CLL cases constitutively expressed HMW-BCGF R and showed a marked proliferative response to HMW-BCGF in [3H]TdR incorporation assays as well as colony assays. Similarly, HCL cells, PLL cells, and activated normal B cells expressed functional HMW-BCGF R, as determined by ligand binding assays using 125I-HMW-BCGF, [3H]TdR incorporation assays, and reactivity with BA-5 MAb. Scatchard analyses indicated the existence of approximately 3,000 HMW-BCGF R/cell on HMW-BCGF responsive CLL cells with an apparent Ka value of 4.6 X 10(7) M-1. The concentrations of HMW-BCGF required for maximum stimulation of CLL cells were two to three orders of magnitude lower than those needed for half maximal receptor occupancy, indicating that only a small fraction of HMW-BCGF R need to be occupied to stimulate leukemic CLL B cells. Crosslinking of surface bound 125I-HMW-BCGF (60 kD) with the bivalent crosslinker DTSSP to its binding site on fresh CLL cells identified a 150-kD HMW-BCGF/HMW-BCGF R complex, suggesting an apparent molecular weight of 90 kD for the receptor protein. The growth stimulatory effects of HMW-BCGF on clonogenic CLL cells did not depend on accessory cells or costimulant factors. The anti-HMW-BCGF R monoclonal antibody BA-5 disrupted HMW-BCGF/HMW-BCGF R interactions at the level of clonogenic CLL cells and inhibited HMW-BCGF-stimulated CLL colony formation in vitro. To our knowledge, this study represents the first detailed analysis of expression, function, and structure of HMW-BCGF R on B lineage CLL cells. Images

Uckun, F M; Fauci, A S; Chandan-Langlie, M; Myers, D E; Ambrus, J L

1989-01-01

98

Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma cell leukemia  

PubMed Central

Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or plasma cell myeloma, are typically characterized by production of a monoclonal heavy and/or light chain immunoglobulin. We present a case of a secondary plasma cell leukemia arising from plasma cell myeloma with dual expression of lambda and kappa light chains along with aberrant expression of CD33, CD20, and dim CD56. This case emphasizes the importance of recognizing aberrant immunophenotypes in plasma cell leukemias and represents the first reported case of biclonal light chain expression in a secondary plasma cell leukemia.

Gentry, Michael; Pettenati, Mark; Pang, Changlee S

2013-01-01

99

Establishment and culture of leukemia-lymphoma cell lines.  

PubMed

The advent of continuous human leukemia-lymphoma cell lines as a rich resource of abundant, accessible, and manipulable living cells has contributed significantly to a better understanding of the pathophysiology of hematopoietic tumors. The first leukemia-lymphoma cell lines were established in 1963 and since then large numbers of new cell lines have been described. The major advantages of continuous leukemia-lymphoma cell lines are the unlimited supply and worldwide availability of identical cell material and the infinite viable storability in liquid nitrogen. These cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro under preservation of most cellular features, and by specific genetic alterations. Here some of the more promising techniques for establishing new leukemia-lymphoma cell lines and the basic principles for culturing these cells are described. Several clinical and cell culture parameters might have some influence on the success rate, e.g., choice of culture medium and culture conditions, specimen site of the primary cells, and status of the patient at the time of sample collection. PMID:21516408

Drexler, Hans G

2011-01-01

100

Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.  

PubMed Central

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis. Images

Shimoyama, M; Kagami, Y; Shimotohno, K; Miwa, M; Minato, K; Tobinai, K; Suemasu, K; Sugimura, T

1986-01-01

101

Autologous leukemia-specific T-cell-mediated lymphocytotoxicity in patients with acute myelogenous leukemia  

PubMed Central

Short-term culture of acute myelogenous leukemia patient's remission lymphocytes with inactivated autologous leukemic blast cells plus allogeneic lymphocytes, generated effector T lymphocytes which were cytotoxic for the specific autologous blast cell in 11 of 14 patients studied. Experiments using Daudi and Molt 4 lymphoblastoid cell lines as third-party helper cell suggest that an HLA D locus incompatability is necessary to provide effective help in this system. Cold target inhibition experiments, crossover studies between pairs of patients, and experiments with allogeneic leukemic blast cells as priming stimulus suggest that the target antigen is only present on the specific autologous blast cell.

1978-01-01

102

Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro.  

PubMed

Physalins B and F were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Both physalin B and physalin F inhibited the growth of several human leukemia cells: K562 (erythroleukemia), APM1840 (acute T lymphoid leukemia), HL-60 (acute promyelocytic leukemia), KG-1 (acute myeloid leukemia), CTV1 (acute monocytic leukemia) and B cell (acute B lymphoid leukemia). Physalin F showed a stronger activity against these leukemia cells than physalin B, especially against acute myeloid leukemia (KG-1) and acute B lymphoid leukemia (B cell). From the structural features, the active site seems to be the functional epoxy group for physalin F and the double bond for physalin B located at carbon 5 and 6; the former is much more active than the latter as regards anti-leukemic effects. PMID:1503404

Chiang, H C; Jaw, S M; Chen, P M

103

Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells  

Microsoft Academic Search

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also

Mascha Binder; Barbara Léchenne; Ramesh Ummanni; Christan Scharf; Stefan Balabanov; Maria Trusch; Hartmut Schlüter; Ingke Braren; Edzard Spillner; Martin Trepel; Donald Gullberg

2010-01-01

104

Differential adhesion pattern of B cell chronic lymphocytic leukemia cells.  

PubMed

Binding of B cell chronic lymphocytic leukemia (B-CLL) cells to other cells and to extracellular matrices influences the pathophysiology and the clinical presentation of the B-CLL disease. It is still unknown which adhesion pathways regulate the traffic of B-CLL cells within distinct histologic compartments of lymphoid organs. In addition, it is not yet clarified which mechanisms mediate the intercellular adhesion of B-CLL cells. The present study sought to identify the mechanisms that are involved in the binding of B-CLL cells to secondary lymphoid organs in situ and in the homotypic aggregation of these cells. B-CLL cells specifically bound to germinal centers of normal human tonsils via the adhesion pair integrin alpha4beta1/vascular cell adhesion molecule-1 (VCAM-1). Among a large panel of antibodies tested only mAbs against CD19 induced homotypic adhesion of B-CLL cells via the adhesion molecules integrin alphaL (leukocyte function antigen-1 (LFA-1)), intercellular adhesion molecule-1 (ICAM-1) and CD21. Anti-CD19-induced aggregation required protein synthesis. We hypothesize that the observed heterotypic and homotypic adhesion of B-CLL cells reflects the ability of these leukemic cells to migrate in vivo. PMID:9436923

Behr, S I; Korinth, D; Schriever, F

1998-01-01

105

Glucotropaeolin and myrosinase production in hairy root cultures of Tropaeolum majus  

Microsoft Academic Search

We obtained callus, cell suspension and hairy root cultures of Tropaeolum majus and we demonstrated their ability to produce\\u000a glucotropaeolin and myrosinase. In hairy roots glucotropaeolin content and myrosinase activity were higher in comparison with\\u000a callus, cell suspension and leaves of intact plants. In hairy root cultures the highest glucotropaeolin contents were detected\\u000a on the 9th day of culture. In

Marzena Wielanek; Henryk Urbanek

1999-01-01

106

Chaperone Rich Cell Lysate (CRCL) Vaccine for Chronic Myelogenous Leukemia.  

National Technical Information Service (NTIS)

We evaluated whether immunization of mice with dendritic cells (DCs) loaded with 12B1 murine bcr-abl+ leukemia -derived chaperone-rich cell lysates (CRCL) induced BCR-ABL specific immune responses in vivo. We found that splenocytes from mice immunized wit...

E. Katsanis

2004-01-01

107

Testican 3 expression in adult T-cell leukemia  

Microsoft Academic Search

Adult T-cell leukemia (ATL) is an aggressive disease characterized by visceral invasion, and ATL regulates matrix metalloproteinase (MMP) activities of the endothelial cells. The controlling system of MMP activities in ATL is regulated by various factors such as Emmprin and tissue inhibitor of MMP. In this study, we demonstrated that Testican 3 expression in ATL decreased the activity of MMP.

Mikio Kamioka; Jun Imamura; Naoki Komatsu; Masanori Daibata; Tetsuro Sugiura

2009-01-01

108

A High Throughput Screening Algorithm for Leukemia Cells  

Microsoft Academic Search

This paper presents a high throughput screening algorithm for leukemia cells that has been designed, implemented, and tested. It performs a recursive image segmentation technique, row-wise and column-wise, on edge detected cell image. The recursive image segmentation successfully eliminates background pixels from foreground pixels by only segmenting image sections that contain relevant pixels. Then, the algorithm generates a boundary box

Brinda Prasad; Jong-sook Iris Choi; Wael M. Badawy

2006-01-01

109

Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia  

PubMed Central

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-? combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients.

El Hajj, Hiba; El-Sabban, Marwan; Hasegawa, Hideki; Zaatari, Ghazi; Ablain, Julien; Saab, Shahrazad T.; Janin, Anne; Mahfouz, Rami; Nasr, Rihab; Kfoury, Youmna; Nicot, Christophe; Hermine, Olivier; Hall, William

2010-01-01

110

FMNL1 promotes proliferation and migration of leukemia cells.  

PubMed

The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation. PMID:23801653

Favaro, Patricia; Traina, Fabiola; Machado-Neto, João Agostinho; Lazarini, Mariana; Lopes, Matheus Rodrigues; Pereira, João Kleber Novais; Costa, Fernando Ferreira; Infante, Elvira; Ridley, Anne J; Saad, Sara Teresinha Olalla

2013-06-25

111

Secondary metabolism of hairy root cultures in bioreactors  

Microsoft Academic Search

Summary  In vitro cultures are being considered as an alternative to agricultural processes for producing valuable secondary metabolites.\\u000a Most efforts that use differentiated cultures instead of cell suspension cultures have focused on transformed (hairy) roots.\\u000a Bioreactors used to culture hairy roots can be roughly divided into three types: liquid-phase, gas-phase, or hybrid reactors\\u000a that are a combination of both. The growth

Yoojeong Kim; Barbara E. Wyslouzil; Pamela J. Weathers

2002-01-01

112

Cell-based immune therapy shows promise in leukemia patients  

Cancer.gov

Memorial Sloan-Kettering investigators report that genetically modified immune cells have shown great promise in killing the cancer cells of patients with relapsed B cell acute lymphoblastic leukemia (ALL). In fact, all five of the patients who have received the new therapy – known as targeted immunotherapy – have gone into complete remission, with no detectable cancer cells. The results of this ongoing clinical trial are reported online on March 20 in the journal Science Translational Medicine.

113

Acute myeloid leukemia stem cells and CD33-targeted immunotherapy  

PubMed Central

Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute myeloid leukemia (AML) are a paradigm of such a strategy. Heterogeneity of these cells was suggested by clonal analyses indicating the existence of both leukemias resulting from transformed multipotent CD33? stem cells as well others arising from, or predominantly involving, committed CD33+ myeloid precursors. The latter leukemias, which may be associated with an intrinsically better prognosis, offer a particularly attractive target for stem cell-directed therapies. Targeting the CD33 differentiation antigen with gemtuzumab ozogamicin was the first attempt of such an approach. Emerging clinical data indicate that gemtuzumab ozogamicin is efficacious not only for acute promyelocytic leukemia but, in combination with conventional chemotherapy, also for other favorable- and intermediate-risk AMLs, providing the first proof-of-principle evidence for the validity of this strategy. Herein, we review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis for success and failure in various AML subsets.

Appelbaum, Frederick R.; Estey, Elihu H.; Bernstein, Irwin D.

2012-01-01

114

Prognostic value of Th17 cells in acute leukemia.  

PubMed

Th17 cells and their effector cytokines have emerged as important mediators in inflammatory and autoimmune diseases and serve as an ambitious field in current immunology research. Recent studies suggest a potential impact of Th17 cells on solid tumors but relatively little is known about their contribution in hematological malignancies. The current study was designed to investigate the possible involvement and clinical significance of circulating Th17 cells in acute leukemia. Flow cytometry was used to analyze percentages of Th17 cells in peripheral blood mononuclear cells from 93 acute leukemia patients (ALL, n = 30; AML, n = 63) and 40 healthy volunteers. Serum levels of IL-17 and IL-21 were measured using enzyme-linked immunosorbent assay. Circulating Th17 cells were increased in patients with acute leukemia (2.88 ± 0.65% and 2.90 ± 0.57% in ALL and AML patients, respectively) and were significantly higher than in healthy controls (1.10 ± 0.28%; P = 0.001). Furthermore, pretreatment Th17 cells were reduced significantly in patients who achieved complete remission after induction therapy (2.25 ± 0.44 % and 1.63 ± 0.27% in ALL and AML patients, respectively, P < 0.0001). Serum levels of IL-17 and IL-21 were significantly elevated in acute leukemia patients. Kaplan-Meier curves revealed a significantly longer overall survival in patients with high Th17 levels (P = 0.029 and P = 0.027 for ALL and AML, respectively). In the multivariate analysis, Th17 cells retained statistical significance for overall survival in patients with ALL (OR 0.331; P = 0.043) and AML (OR 0.489; P = 0.032). These results strongly suggest Th17 cells as a powerful new prognostic determinant which could serve as a potential therapeutic target to modulate anti-tumor response in acute leukemia patients. PMID:24085544

Abousamra, Nashwa Khairat; Salah El-Din, Manal; Helal, Randah

2013-10-02

115

T-cell receptor tau delta +/CD3+4-8-T- cell acute lymphoblastic leukemias: a distinct subgroup of leukemias in children. A report of five cases.  

PubMed

In a 10-year study of T-cell acute lymphoblastic leukemias (T-ALL) in children, we have identified five cases expressing the T-cell receptor tau delta (TCR tau delta). The incidence (26%) of TCR tau delta+T-cell leukemias in our material was high. Clinically, the TCR tau delta+ leukemias represented a distinct subgroup of T-cell leukemias. Mean age at onset of disease, 1.8 years, was remarkably low for mature T-cell leukemias. White blood cell counts were high, lymph node enlargements were discrete, and no mediastinal tumors were seen. Four of five TCR tau delta+ leukemias carried rearrangements of the C tau 2 gene, and transcribed the T-early alpha genetic element. PMID:1826854

Alfsen, G C; Beiske, K; Holte, H; Hovig, E; Deggerdal, A; Sandlie, I; Widing, E; Slørdahl, S; Klepper, L K; Sizoo, W

1991-05-01

116

Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic leukemia and tyrosine kinase inhibitor therapy  

PubMed Central

Leukemia stem cells (LSCs), which constitute a minority of the tumor bulk, are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal. The presence of LSCs has been demonstrated in acute lymphoblastic leukemia (ALL), of which ALL with Philadelphia chromosome-positive (Ph+). The use of imatinib, a tyrosine kinase inhibitor (TKI), as part of front-line treatment and in combination with cytotoxic agents, has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph+ ALL. New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations. An important recent addition to the arsenal against Ph+ leukemias in general was the development of novel TKIs, such as nilotinib and dasatinib. However, in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells. None of the TKIs in clinical use target the LSC. Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs. Allogeneic stem cell transplantation (SCT) remains the only curative treatment available for these patients. Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations. Hence, TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy. Better understanding the biology of Ph+ ALL will open new avenues for effective management. In this review, we highlight recent findings relating to the question of LSCs in Ph+ ALL.

Thomas, Xavier

2012-01-01

117

Donor Cell Leukemia in Umbilical Cord Blood Transplant Patients  

PubMed Central

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patient's diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patient's disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patient's presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.

Crow, Jennifer; Youens, Kenneth; Michalowski, Susan; Perrine, Gail; Emhart, Cassandra; Johnson, Felicia; Gerling, Amy; Kurtzberg, Joanne; Goodman, Barbara K.; Sebastian, Siby; Rehder, Catherine W.; Datto, Michael B.

2010-01-01

118

Viral proteins expressed on the surface of murine leukemia cells.  

PubMed Central

Leukemic cells of AKR mice contain as constituents of their membranes the murine leukemia virus envelope protein gp70 and the precursor polyprotein of the viral internal (core) structural proteins. Both gp70 and the core polyprotein are represented on the cell surface as glycoproteins, as evidenced by incorporation of [3H]glucosamine into their structure and the binding of these proteins to lectins. The glycosylated core polyprotein exists in at least two serologically distinguishable forms: the 95,000-dalton polyprotein reacts with antisera prepared against the viral proteins p30, p12, and p10, whereas the 85,000-dalton polyprotein reacts with antisera prepared against the viral proteins p30 and p12, but not p10. Additional heterogeneity in these cell surface polyproteins has been observed wtih leukemias induced by exogenous leukemia viruses. Spontaneous leukemia cells of AKR mice invariably express gp70 and the core polyprotein on their cell surface; normal thymocytes of young AKR mice express gp70, but not the core polyprotein on their surface.

Ledbetter, J; Nowinski, R C; Emery, S

1977-01-01

119

Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells  

Microsoft Academic Search

Farnesyltransferase inhibitors (FTIs) are currently under investigation for leukemia treatment. We evaluated the FTI manumycin A (manumycin) in two myeloid leukemia cell lines (U937 and HL-60). Manumycin induced nitric oxide production and apoptosis of the leukemia cells. Nitric oxide or other reactive oxygen species may induce oxidative DNA damage, and the number of apurinic sites increased after manumycin treatment, which

M She; J Pan; L Sun; S-C Jim Yeung

2005-01-01

120

Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells  

Microsoft Academic Search

Mitogen-activated protein (MAP) kinase appears to be one of the key regulators of cell proliferation and differentiation. Very little, however, has been revealed as to how MAP kinase is involved in leukemogenesis. We have studied the activation of the MAP kinase pathway in 100 human primary leukemia cells including 73 acute myelogenous leukemias (AMLs). Forty acute leukemia samples (40% of

M Towatari; H Iida; M Tanimoto; H Iwata; M Hamaguchi; H Saito

1997-01-01

121

Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors  

PubMed Central

Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML.

Sukhai, Mahadeo A.; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C.; Lee, Anna Y.; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E.; Spagnuolo, Paul A.; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S.; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y.; Corey, Seth J.; Eaves, Connie; Minden, Mark D.; Wang, Jean C.Y.; Dick, John E.; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D.

2012-01-01

122

Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors.  

PubMed

Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. PMID:23202731

Sukhai, Mahadeo A; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C; Lee, Anna Y; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E; Spagnuolo, Paul A; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y; Corey, Seth J; Eaves, Connie; Minden, Mark D; Wang, Jean C Y; Dick, John E; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D

2012-12-03

123

Ponicidin Inhibits Monocytic Leukemia Cell Growth by Induction of Apoptosis  

PubMed Central

In this study two monocytic leukemia cell lines, U937 and THP-1 cells, were used to investigate the anti-proliferation effects caused by ponicidin. Cell viability was measured by an MTT assay. Cell apoptosis was assessed by flow cytometry as well as DNA fragmentation analysis. Cell morphology was observed using an inverted microscope and Hoechst 33258 staining. RT-PCR and Western blot analysis were used to detect survivin as well as Bax and Bcl-2 expressions after the cells were treated with different concentrations of ponicidin. The results revealed that ponicidin could inhibit the growth of U937 and THP-1 cells significantly by induction of apoptosis. The suppression was in both time- and dose-dependent manner. Marked morphological changes of cell apoptosis were observed clearly after the cells were treated with ponicidin for 48?72 h. RT-PCR and Western blot analysis demonstrated that both survivin and Bcl-2 expressions were down-regulated remarkably while Bax expression remained constant before and after apoptosis occurred. We therefore conclude that ponicidin has significant anti-proliferation effects by inducing apoptosis on leukemia cells in vitro, downregulation of survivin as well as Bcl-2 expressions may be the important apoptosis inducing mechanisms. The results suggest that ponicidin may serve as potential therapeutic agent for leukemia.

Liu, Jia-Jun; Zhang, Yong; Guang, Wei-Bin; Yang, Hong-Zhi; Lin, Dong-Jun; Xiao, Ruo-Zhi

2008-01-01

124

High-Output Cardiac Failure Revealing Primary Plasma Cell Leukemia  

PubMed Central

High-output cardiac failure in multiple myeloma (MM) is related to arteriovenous shunting in bone infiltrate disease. We describe such a complication in a patient with primary plasma cell leukemia (pPCL) without bone disease. We review the mechanisms that could be involved. As previously described, traditional cardiac failure therapy is not effective. pPCL therapy should not be delayed.

Chaoui, Driss; Gallet, Bruno; Genet, Philippe; Mbungani, Babette; Al Jijakli, Ahmad; Arakelyan, Nina; Mesbah, Louisa; Sutton, Laurent

2013-01-01

125

Common Cell-Surface Antigen Associated with Murine and Feline C-Type RNA Leukemia Viruses  

Microsoft Academic Search

A new common cell-surface antigen associated with murine and feline C-type RNA leukemia viruses was demonstrated by the use of rabbit antiserum against feline leukemia virus and the indirect membrane immunofluorescence test. Common cell-surface antigen was found in all leukemias of all strains of mice tested, in normal lymphoid tissues of Gross-positive (high incidence of leukemia) mouse strains AKR, AKR\\\\cdot

Takashi Yoshiki; Robert C. Mellors; William D. Hardy

1973-01-01

126

Myeloid/natural killer cell precursor acute leukemia diagnosed by cell marker analysis.  

PubMed

We report a case of myeloid/natural killer cell precursor acute leukemia. A 68-year-old man was diagnosed as having lymphoma in his neck, and was referred to our department for further examination and treatment. After admission, blastoid-cells appeared and increased rapidly in his peripheral blood. Cell marker analysis revealed that the blastoid-cells expressed CD7, CD56, CD33, and CD34. He was then diagnosed with myeloid/natural killer cell precursor leukemia. This form of leukemia was recently established as a distinct disease entity. Further clinicopathological evaluation and the establishment of treatment are necessary. PMID:23823098

Miura, Rika; Yoshimi, Mayumi; Kikuchi, Yuji; Takahashi, Tsuyoshi

2013-06-01

127

Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance.  

PubMed

T-cell acute lymphoblastic leukemia (T-ALL) is associated with a significant risk of disease relapse, but the biological basis for relapse is poorly understood. Here, we identify leukemiainitiating cells (L-ICs) on the basis of functional assays and prospective isolation and report a role for L-ICs in T-ALL disease and relapse. Long-term proliferation in response to NOTCH1 activating signals in OP9-DL1 coculture system or capacity to initiate leukemia in xenografts by the CD7(+)CD1a(-) subset of primary T-ALL samples was superior to other subsets, refining the identity of T-ALL L-ICs. T-ALL engraftment was improved in nonobese diabetic/severe combined immunodeficiency (NOD/scid)IL2R?(null) (NSG) mice compared with NOD/scid with anti-CD122 treatment (NS122), but both showed changes in leukemia immunophenotype. Clonal analysis of xenografts using the TCRG locus revealed the presence of subclones of T-ALL L-ICs, some of which possess a selective growth advantage and correlated with the capacity of CD7(+)CD1a(+) xenograft cells to engraft secondary NSG mice. Treatment of high-risk T-ALL xenografts eliminated CD1a(+) T-ALL cells, but CD1a(-) cells were resistant and their number was increased. Our results establish that primary CD1a(-) T-ALL cells are functionally distinct from CD1a(+) cells and that the CD7(+)CD1a(-) subset is enriched for L-IC activity that may be involved in mediating disease relapse after therapy. PMID:20810926

Chiu, Priscilla P L; Jiang, Hong; Dick, John E

2010-09-01

128

High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias  

Microsoft Academic Search

In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-PrkdcscidIL2rgtmlWjl\\/SzJ (NOD-severe combined immune deficient (scid) IL2rg?\\/?) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations

S Morisot; A S Wayne; O Bohana-Kashtan; I M Kaplan; C D Gocke; R Hildreth; M Stetler-Stevenson; R L Walker; S Davis; P S Meltzer; S J Wheelan; P Brown; R J Jones; L D Shultz; C I Civin

2010-01-01

129

Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission  

ClinicalTrials.gov

B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

2013-06-14

130

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia  

Microsoft Academic Search

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg\\/kg), etoposide (40 mg\\/kg), and cytosine arabinoside (3 g\\/m2 × 4) (BEA regimen) was used for

H Gondo; M Harada; T Miyamoto; K Takenaka; K Tanimoto; S Mizuno; T Fujisaki; K Nagafuji; S Hayashi; T Eto; S Taniguchi; K Akashi; N Harada; K Yamasaki; T Shibuya; E Matsuishi; Y Ohno; S Makino; Y Takamatsu; M Murakawa; T Teshima; Y Hirota; T Okamura; N Kinukawa; S Inaba; Y Niho

1997-01-01

131

Plasmacytoid Dendritic Cell Leukemia with Potent Antigen-Presenting Ability  

Microsoft Academic Search

We report 2 patients with plasmacytoid dendritic cell leukemia (pDCL) expressing CD4, CD56, CD33, CD36, HLA-DR, CD123, CD86 and CD83 in the absence of lineage markers (myeloid, B, T or natural killer cells) except for CD33. Culturing leukemic blasts of both cases with IL-3 for 4 days increased the expression of surface molecules associated with antigen presentation, e.g. CD1a and

Miwako Narita; Takashi Kuroha; Norihiro Watanabe; Shigeo Hashimoto; Junjiro Tsuchiyama; Nozomi Tochiki; Anri Saitoh; Noriyuki Satoh; Tatsuo Furukawa; Ken Toba; Ichiro Fuse; Yoshifusa Aizawa; Masuhiro Takahashi

2008-01-01

132

Complete Suppression of in vivo Growth of Human Leukemia Cells by Specific Immunotoxins: Nude Mouse Models  

Microsoft Academic Search

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undesirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens

Hideki Hara; Ben K. Seon

1987-01-01

133

[Hematopoietic stem cell transplantation for treatment of acute leukemia].  

PubMed

Recently, hematopoietic stem cell transplantation has been diversified and classified into several types of transplants, including allogeneic bone marrow, peripheral blood stem cell and cord blood stem cell transplantation (BMT, PBSCT, CBSCT), from related or unrelated donors. In addition, autologous BMT or PBSCT can be used to facilitate hematologic reconstitution after marrow-ablative therapy for hematologic malignancies. At least 50% of patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) can be cured by treatment with allogeneic BMT. Autologous BMT has been studied in comparison with allogeneic BMT or intensive chemotherapy in the treatment of AML and ALL. A series of large-scale prospective randomized studies have provided controversial results: relapse rates are significantly low, but treatment-related mortality is significantly high, after allogeneic or autologous BMT as compared to intensive chemotherapy. At present, it is somewhat difficult to determine which treatment modality is indicated as a postremission therapy for AML and ALL. Therefore, risk factors such as leukemia subtype, age, karyotype, and initial response should be taken into consideration when deciding on a postremission therapy. In the 1990's, the use of autologous PBSCT has been replacing autologous BMT, as autologous PBSCT has several advantages over autologous BMT. Consequently, allogeneic PBSCT has come to be increasingly used instead of allogeneic BMT in the treatment of leukemia. Recent clinical data clearly indicate that allogeneic PBSCT can be used as an alternative to allogeneic BMT. With well-designed clinical trials, the places, of allogeneic or autologous BMT and PBSCT will be clarified in the treatment strategy for acute leukemia. PMID:10500524

Harada, M

1999-09-01

134

Cell-free entry of human T-cell leukemia virus type 1 to mouse cells.  

PubMed

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia and HTLV-1-associated myelopathy / tropical spastic paraparesis. Recently we infected newborn mice by inoculating HTLV-1-producing human cells, and found that T-cells, B-cells and granulocytes were infected in vivo. To understand the mechanism of viral-cell interaction and the pathogenesis of HTLV-1 using the mouse model, it is important to clarify the cellular tropism using a cell-free HTLV-1 transmission system. We employed a highly transmissible cell-free HTLV-1 produced by a feline kidney cell line, c77, and studied the susceptibility of 9 kinds of mouse cell lines, EL4, RLm1, CTLL-2, J774.1, DA-1, Ba / F3, WEHI-3, NIH3T3 and B1, and two kinds of human cell lines, Molt-4 and Hut78. HTLV-1 proviral sequence was found by PCR in all 9 mouse cell lines as well as in 2 human cell lines and viral entry was blocked with sera from an HTLV-1 carrier and an adult T-cell leukemia patient. Unexpectedly, mouse cell lines EL4 and RLm1 and human cell lines Molt-4 and Hut78 showed similar efficiency for viral entry. These results suggest a wide distribution of HTLV-1 receptor in mouse cells. PMID:11346463

Feng, R; Kabayama, A; Uchida, K; Hoshino, H; Miwa, M

2001-04-01

135

Acute lymphocytic leukemia (ALL)  

MedlinePLUS

ALL; Acute childhood leukemia; Cancer - acute childhood leukemia (ALL); Leukemia - acute childhood (ALL) ... Acute lymphocytic leukemia (ALL) occurs when the the body produces a large number of immature white blood cells, called ...

136

Interleukin 1 gene expression in adult T cell leukemia.  

PubMed Central

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations. Images

Wano, Y; Hattori, T; Matsuoka, M; Takatsuki, K; Chua, A O; Gubler, U; Greene, W C

1987-01-01

137

Spontaneous Cell Fusion of Acute Leukemia Cells and Macrophages Observed in Cells with Leukemic Potential12  

PubMed Central

Cell fusion plays a well-recognized physiological role during development, while its function during progression is still unclear. Here, we show that acute myeloid leukemia (AML) cells spontaneously fused with murine host cells in vivo. AML cells fused in most cases with mouse macrophages. Other targets of AML cell fusion were dendritic and endothelial cells. Cytogenetic and molecular analysis revealed that successive recipients conserved detectable amounts of parental DNA. Moreover, in a mouse AML1-ETO model where female AML1-ETO-leukemic cells, expressing CD45.2, were injected in congenic CD45.1 male mice AML cells, we found hybrid cells expressing both allelic types of CD45 and XXY set of sexual chromosomes. More importantly, the fusion protein AML1-ETO was transferred in the hybrid cells. When sorted hybrid cells were reinjected in a secondary recipient, they gave rise to leukemia with 100% penetrance and similar time of onset of leukemic cells. Our data indicate that in vivo fusion of cancer cells with host cells may be a mechanism of gene transfer for cancer dissemination and suggest that fused cells may be used to identify still unrecognized leukemogenic genes that are conserved in hybrid cells and able to perpetuate leukemia in vivo.

Martin-Padura, Ines; Marighetti, Paola; Gregato, Giuliana; Agliano, Alice; Malazzi, Omar; Mancuso, Patrizia; Pruneri, Giancarlo; Viale, Andrea; Bertolini, Francesco

2012-01-01

138

Spontaneous cell fusion of acute leukemia cells and macrophages observed in cells with leukemic potential.  

PubMed

Cell fusion plays a well-recognized physiological role during development, while its function during progression is still unclear. Here, we show that acute myeloid leukemia (AML) cells spontaneously fused with murine host cells in vivo. AML cells fused in most cases with mouse macrophages. Other targets of AML cell fusion were dendritic and endothelial cells. Cytogenetic and molecular analysis revealed that successive recipients conserved detectable amounts of parental DNA. Moreover, in a mouse AML1-ETO model where female AML1-ETO-leukemic cells, expressing CD45.2, were injected in congenic CD45.1 male mice AML cells, we found hybrid cells expressing both allelic types of CD45 and XXY set of sexual chromosomes. More importantly, the fusion protein AML1-ETO was transferred in the hybrid cells. When sorted hybrid cells were reinjected in a secondary recipient, they gave rise to leukemia with 100% penetrance and similar time of onset of leukemic cells. Our data indicate that in vivo fusion of cancer cells with host cells may be a mechanism of gene transfer for cancer dissemination and suggest that fused cells may be used to identify still unrecognized leukemogenic genes that are conserved in hybrid cells and able to perpetuate leukemia in vivo. PMID:23226099

Martin-Padura, Ines; Marighetti, Paola; Gregato, Giuliana; Agliano, Alice; Malazzi, Omar; Mancuso, Patrizia; Pruneri, Giancarlo; Viale, Andrea; Bertolini, Francesco

2012-11-01

139

Donor cell leukemia: insight into cancer stem cells and the stem cell niche  

Microsoft Academic Search

Donor cell leukemia (DCL) is a rare compli- cation of hematopoietic cell transplanta- tion (HCT). Its incidence has been re- ported between 0.12% and 5%, although the majority of cases are anecdotal. The mechanisms of leukemogenesis in DCL may be distinct from other types of leuke- mia. Possible causes of DCL include on- cogenic alteration or premature aging of transplanted

Catherine M. Flynn; Dan S. Kaufman

2007-01-01

140

Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia\\/Lymphoma  

Microsoft Academic Search

Adult T-cell leukemia\\/lymphoma (ATLL) develops in elderly individuals who have been infected with human T-cell leukemia virus\\u000a type 1 (HTLV-1), and the prognosis for patients with ATLL has been extremely poor. Retrospective studies of allogeneic stem\\u000a cell transplantation (alloSCT) for selected populations of patients have achieved several encouraging results; however, the\\u000a reported incidence of transplantation-related mortality (TRM) have been high,

Jun Okamura; Naokuni Uike; Atae Utsunomiya; Ryuji Tanosaki

2007-01-01

141

OX40 Signaling Renders Adult T-Cell Leukemia Cells Resistant to Fas-Induced Apoptosis  

Microsoft Academic Search

We reported previously that OX40, a member of the tumor necrosis factor receptor family, is expressed constitutively on fresh\\u000a leukemia\\/lymphoma cells isolated from patients with adult T-cell leukemia (ATL). In this study, we tested whether OX40 signaling\\u000a affects the Fas-mediated apoptosis of fresh ATL cells isolated from 7 patients (3 acute type, 3 chronic type, and 1 smoldering\\u000a type). In

Akane Kunitomi; Toshiyuki Hori; Michiyuki Maeda; Takashi Uchiyama

2002-01-01

142

Chronic lymphocytic leukemia: a disease of activated monoclonal B cells  

PubMed Central

B-cell type chronic lymphocytic leukemia (CLL) has long been considered a disease of resting lymphocytes. However cell surface and intracellular phenotypes suggest that most CLL cells are activated cells, although only a small subset progresses beyond the G1 stage of the cell cycle. In addition, traditional teaching says that CLL cells divide rarely, and therefore the buildup of leukemic cells is due to an inherent defect in cell death. However, in vivo labeling of CLL cells indicates a much more active rate of cell birth than originally estimated, suggesting that CLL is a dynamic disease. Here we review the observations that have led to these altered views of the activation state and proliferative capacities of CLL cells and also provide our interpretation of these observations in light of their potential impact on patients.

Damle, Rajendra N.; Calissano, Carlo; Chiorazzi, Nicholas

2010-01-01

143

Adult T-cell Leukemia/Lymphoma: A Retroviral Malady  

PubMed Central

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive leukemia/lymphoma of mature T-lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). At a tertiary healthcare center in South India, a 58-year-old female presented with multiple erythematous, crusted, and umbilicated papules over the body along with cervical lymphadenopathy. The skin biopsy was consistent with cutaneous T-cell lymphoma. Although she responded initially to chemotherapy, the disease relapsed after 3 months, and she developed disseminated infiltrated skin lesions, generalized lymphadenopathy, and leukemia. Due to the unusual clinical findings we did HTLV-1 Enzyme-linked immunosorbent assay (ELISA), which turned out to be positive in high titers. Her mother had died at an early age from a hematological malignancy and her daughter was also found to be seropositive. To the best of our knowledge, this is the first case to be reported from India of the chronic type of ATLL associated with mother-to-child transmission of HTLV-1 in two generations. This case also emphasizes that the chronic type of ATLL can occur in nonendemic areas like India and should be suspected in nonresponding cases of mycosis fungoides. It should be kept in mind that the chronic type often presents without hypercalcemia or the characteristic ‘flower cells’ in the peripheral smear.

Khader, Anza; Shaan, Mohamed; Sasidharanpillai, Saritha; Pakran, Jaheersha; Rajan, Uma

2012-01-01

144

The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia  

Microsoft Academic Search

We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15–68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed

E Sloand; R W Childs; S Solomon; A Greene; N S Young; A J Barrett

2003-01-01

145

Telomerase is limiting the growth of acute myeloid leukemia cells.  

PubMed

Telomeres play an important role in the proliferation and senescence of normal and malignant cells. To test the role of telomerase in acute myeloid leukemia (AML), we expressed the telomerase reverse transcriptase (hTERT) gene, a dominant-negative hTERT (DN-hTERT) (D868A, D869A) gene, or a gene encoding green fluorescence protein (GFP) in the leukemia cell line K562 and in primary AML cells from different patients, using retroviral vectors. Cells transduced with hTERT exhibited elevated levels of telomerase activity compared to GFP controls, whereas cells expressing DN-hTERT had decreased telomerase activity. K562 populations transduced with DN-hTERT showed reduced clonogenicity, telomere dysfunction and increased numbers of apoptotic cells compared to GFP- or hTERT-transduced cells. Two of four clones transduced with DN-hTERT died after 30 and 53 population doublings, respectively. Transduced AML cells were tested in primary colony-forming unit (CFU) and suspension culture assays. Relative to hTERT- and GFP-transduced controls, AML cells transfected with DN-hTERT produced fewer CFU and showed lower engraftment after transplantation into sublethally irradiated beta(2)-m(-/-) nonobese diabetic/severe combined immunodeficient mice. We conclude that telomerase is limiting the growth of the leukemic cell line K562 and primary AML progenitor cells. Our data warrant further studies of the therapeutic use of telomerase inhibitors in AML. PMID:14562114

Röth, A; Vercauteren, S; Sutherland, H J; Lansdorp, P M

2003-12-01

146

Racemic Etodolac is cytotoxic and cytostatic for B-cell precursor acute lymphoblastic leukemia cells.  

PubMed

Several epidemiological studies have provided evidence that administration of nonsteroidal anti-inflammatory drugs (NSAIDs) could have a prophylactic effect against some cancers such as sporadic colorectal cancer and leukemia. Indeed, various NSAIDs have been shown to induce apoptosis in malignant cells. We evaluated the effect of racemic Etodolac on proliferation and cell survival in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Etodolac decreased survival of Nalm-16 and Nalm-6 BCP-ALL cell lines and also decreased cell proliferation in Nalm-16 cell line. Ours findings indicate, for the first time to our knowledge, that Etodolac is cytotoxic and cytostatic for BCP-ALL cells. PMID:18993025

de Souza Thiago, Leandro; da Costa, Elaine Sobral; Lopes, Daiana Vieira; Borojevic, Radovan

2008-10-23

147

Cytotoxic T cells induce proliferation of chronic myeloid leukemia stem cells by secreting interferon-?  

PubMed Central

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia arising from the oncogenic break point cluster region/Abelson murine leukemia viral oncogene homolog 1 translocation in hematopoietic stem cells (HSCs), resulting in a leukemia stem cell (LSC). Curing CML depends on the eradication of LSCs. Unfortunately, LSCs are resistant to current treatment strategies. The host’s immune system is thought to contribute to disease control, and several immunotherapy strategies are under investigation. However, the interaction of the immune system with LSCs is poorly defined. In the present study, we use a murine CML model to show that LSCs express major histocompatibility complex (MHC) and co-stimulatory molecules and are recognized and killed by leukemia-specific CD8+ effector CTLs in vitro. In contrast, therapeutic infusions of effector CTLs into CML mice in vivo failed to eradicate LSCs but, paradoxically, increased LSC numbers. LSC proliferation and differentiation was induced by CTL-secreted IFN-?. Effector CTLs were only able to eliminate LSCs in a situation with minimal leukemia load where CTL-secreted IFN-? levels were low. In addition, IFN-? increased proliferation and colony formation of CD34+ stem/progenitor cells from CML patients in vitro. Our study reveals a novel mechanism by which the immune system contributes to leukemia progression and may be important to improve T cell–based immunotherapy against leukemia.

Schurch, Christian; Riether, Carsten; Amrein, Michael A.

2013-01-01

148

Cytotoxic T cells induce proliferation of chronic myeloid leukemia stem cells by secreting interferon-?.  

PubMed

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia arising from the oncogenic break point cluster region/Abelson murine leukemia viral oncogene homolog 1 translocation in hematopoietic stem cells (HSCs), resulting in a leukemia stem cell (LSC). Curing CML depends on the eradication of LSCs. Unfortunately, LSCs are resistant to current treatment strategies. The host's immune system is thought to contribute to disease control, and several immunotherapy strategies are under investigation. However, the interaction of the immune system with LSCs is poorly defined. In the present study, we use a murine CML model to show that LSCs express major histocompatibility complex (MHC) and co-stimulatory molecules and are recognized and killed by leukemia-specific CD8(+) effector CTLs in vitro. In contrast, therapeutic infusions of effector CTLs into CML mice in vivo failed to eradicate LSCs but, paradoxically, increased LSC numbers. LSC proliferation and differentiation was induced by CTL-secreted IFN-?. Effector CTLs were only able to eliminate LSCs in a situation with minimal leukemia load where CTL-secreted IFN-? levels were low. In addition, IFN-? increased proliferation and colony formation of CD34(+) stem/progenitor cells from CML patients in vitro. Our study reveals a novel mechanism by which the immune system contributes to leukemia progression and may be important to improve T cell-based immunotherapy against leukemia. PMID:23401488

Schürch, Christian; Riether, Carsten; Amrein, Michael A; Ochsenbein, Adrian F

2013-02-11

149

The role of the segmentation gene hairy in Tribolium  

PubMed Central

Hairy stripes in Tribolium are generated during blastoderm and germ band extension, but a direct role for Tc-h in trunk segmentation was not found. We have studied here several aspects of hairy function and expression in Tribolium, to further elucidate its role. First, we show that there is no functional redundancy with other hairy paralogues in Tribolium. Second, we cloned the hairy orthologue from Tribolium confusum and show that its expression mimics that of Tribolium castaneum, implying that stripe expression should be functional in some way. Third, we show that the dynamics of stripe formation in the growth zone is not compatible with an oscillatory mechanism comparable to the one driving the expression of hairy homologues in vertebrates. Fourth, we use parental RNAi experiments to study Tc-h function and we find that mandible and labium are particularly sensitive to loss of Tc-h, reminiscent of a pair-rule function in the head region. In addition, lack of Tc-h leads to cell death in the gnathal region at later embryonic stages, resulting in a detachment of the head. Cell death patterns are also altered in the midline. Finally, we have analysed the effect of Tc-h knockdown on two of the target genes of hairy in Drosophila, namely fushi tarazu and paired. We find that the trunk expression of Tc-h is required to regulate Tc-ftz, although Tc-ftz is itself also not required for trunk segmentation in Tribolium. Our results imply that there is considerable divergence in hairy function between Tribolium and Drosophila. Electronic supplementary material The online version of this article (doi:10.1007/s00427-008-0240-1) contains supplementary material, which is available to authorized users.

Aranda, Manuel; Marques-Souza, Henrique; Bayer, Till

2008-01-01

150

Acute leukemia after successful chemotherapy for oat cell carcinoma  

SciTech Connect

A report of acute myelomonocytic leukemia following successful therapy for oat cell carcinoma is presented. The patient had been treated with extensive cytotoxic and radiation therapy, and was without clinical evidence of disease at one year follow-up. Eighteen months later, a peripheral smear revealed numerous blasts with monocytoid characteristics. This unusual presentation is discussed and compared with several other cases appearing in the recent literature.

Rose, V.L.; Keppen, M.D.; Eichner, E.R.; Pitha, J.V.; Murray, J.L.

1983-01-01

151

Allogeneic hematopoietic stem cell transplantation for adult acute lymphocytic leukemia  

Microsoft Academic Search

Allogeneic hematopoietic stem cell transplantation (alloHCT) is the single most potent treatment modality to prevent relapse\\u000a in adults with acute lymphocytic leukemia, but its optimal use and timing remains a matter of intense debate and research.\\u000a There is general agreement that patients with clinical features of high risk for relapse should undergo alloHCT in first complete\\u000a remission. However, newer studies

Theis H. Terwey; Theo D. Kim; Renate Arnold

2009-01-01

152

Composite mycosis fungoides and B-cell chronic lymphocytic leukemia  

Microsoft Academic Search

Concordant or composite mycosis fungoides and B-cell chronic lymphocytic leukemia (B-CLL) is exceedingly rare, with only 10 cases previously described to our knowledge. We report a case of a 64-year-old woman who developed generalized erythroderma 5 years after the diagnosis of early stage B-CLL. Over the next 6 years of her clinical course multiple sequential samples of skin, peripheral blood,

Andrea L. Volk; Stephen A. Vannucci; William Cook; Keith A. Thompson; Catherine M. Listinsky

2002-01-01

153

Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells  

Microsoft Academic Search

Accumulating evidence indicates that many human cancers are organized as a cellular hierarchy initiated and maintained by self-renewing cancer stem cells. This cancer stem cell model has been most conclusively established for human acute myeloid leukemia (AML), although controversies still exist regarding the identity of human AML stem cells (leukemia stem cell (LSC)). A major implication of this model is

R Majeti

2011-01-01

154

Selective Inhibition of Leukemia Cell Proliferation by BCR-ABL Antisense Oligodeoxynucleotides  

Microsoft Academic Search

To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells

Cezary Szczylik; Tomasz Skorski; Nicholas C. Nicolaides; Livia Manzella; Lucia Malaguarnera; Donatella Venturelli; Alan M. Gewirtz; Bruno Calabretta

1991-01-01

155

Testican 3 expression in adult T-cell leukemia.  

PubMed

Adult T-cell leukemia (ATL) is an aggressive disease characterized by visceral invasion, and ATL regulates matrix metalloproteinase (MMP) activities of the endothelial cells. The controlling system of MMP activities in ATL is regulated by various factors such as Emmprin and tissue inhibitor of MMP. In this study, we demonstrated that Testican 3 expression in ATL decreased the activity of MMP. Furthermore, we showed that the expression of Testican 3 was regulated by activating transcriptional factor 3 in human T-lymphotropic virus type I-related cell lines. Thus, Testican 3 is a novel regulator to reduce the activity of MMP in ATL. PMID:19144404

Kamioka, Mikio; Imamura, Jun; Komatsu, Naoki; Daibata, Masanori; Sugiura, Tetsuro

2009-01-13

156

Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells.  

PubMed

We analyzed the expression of cell surface antigens and granulocyte colony-stimulating factor (G-CSF) receptors using flow cytometry, the expression of G-CSF mRNA receptor, using reverse transcription (RT)-PCR, and tested the effect of G-CSF on leukemia colony formation. A total of 14 lymphocytic leukemia patients were examined, seven with acute lymphocytic leukemia (ALL), two with adult T-cell leukemia (ATL), two with B-chronic lymphocytic leukemia (CLL), two with chronic myelocytic leukemia in lymphoid blastic crisis (CML-LBC), and one with plasma cell leukemia (PCL). The presence of G-CSF receptors was demonstrated in 4/14 (29%) patients, two with ALL, one with CLL, and one with CML-LBC, and was associated with stimulation of leukemia clonogenic cell growth by G-CSF. In addition, all four positive leukemia cell types expressed typical B-cell antigens. Our results indicated that G-CSF receptors are expressed on some portion of B-lymphoid leukemia and that their receptors are functional as growth stimulators. PMID:10803934

Handa, A; Kashimura, T; Takeuchi, S; Yamamoto, A; Murohashi, I; Bessho, M; Hirashima, K

2000-03-01

157

Preferential eradication of acute myelogenous leukemia stem cells by fenretinide  

PubMed Central

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34+ cells, especially the LSC-enriched CD34+CD38? subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34+ cells but not those from normal CD34+ cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-?B and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide–down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML.

Zhang, Hui; Mi, Jian-Qing; Fang, Hai; Wang, Zhao; Wang, Chun; Wu, Lin; Zhang, Bin; Minden, Mark; Yang, Wen-Tao; Wang, Huan-Wei; Li, Jun-Min; Xi, Xiao-Dong; Chen, Sai-Juan; Zhang, Ji; Chen, Zhu; Wang, Kan-Kan

2013-01-01

158

[An analysis of acute leukemia cells TfR expression in children].  

PubMed

There are a lot of transferrin receptors on the acute leukemia cells. We used the method of "Receptor Radioligand Assay" to determine the numbers of TfR binding sites on leukemia cells from 20 child patients with acute lymphocyte leukemia (ALL) and 9 with acute myeloid leukemia (AML). The results showed the numbers of TfR binding sites of AML cells were higher than those of ALL cells, and the numbers of complete remission group were lower than those of dead or relapse group. This indicated there might be a relationship between the TfR expression and the prognosis. PMID:10684063

Huang, G; Liao, Q; Luo, C; Li, F; Fu, R

1997-03-01

159

Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia  

ClinicalTrials.gov

B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma,; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

2013-06-17

160

Cholesterol regulates VEGFR-1 (FLT-1) expression and signaling in acute leukemia cells.  

PubMed

VEGF receptors 1 (FLT-1) and 2 (KDR) are expressed on subsets of acute myeloid leukemia (AML) and acute lymphoid leukemia cells, in which they induce cell survival, proliferation, and migration. However, little is known about possible cofactors that regulate VEGF receptor expression and activation on leukemia cells. Here we show that cholesterol accumulates in leukemia-rich sites within bone marrow of xenotransplanted severe combined immunodeficient (SCID) mice. Therefore, we hypothesized that cholesterol-rich domains might regulate FLT-1 signaling and chemotaxis of acute leukemias. We then showed that FLT-1 accumulates in discrete cholesterol-rich membrane domains where it associates with caveolin-1 and that placenta growth factor (PlGF)/VEGF stimulation promotes FLT-1 localization in such cholesterol-rich domains. Accordingly, FLT-1 localization and its phosphorylation are abrogated by methyl-?-cyclodextrin (M?CD), which removes cellular cholesterol, and by nystatin, an inhibitor of lipid-raft endocytosis. Mechanistically, cholesterol increases FLT-1 expression and promotes PlGF/VEGF-induced leukemia cells viability and also induces VEGF production by the leukemia cells in vitro. Taken together, we conclude that cholesterol regulates VEGF:VEGFR-1 signaling on subsets of acute leukemias, modulating cell migration, and viability, which may be crucial for disease progression. Finally, we provide evidence obtained from human AML samples that primary leukemia cells accumulate significantly more cholesterol than do normal cells and that cholesterol accumulation correlates with disease aggressiveness. PMID:21209384

Casalou, Cristina; Costa, Ana; Carvalho, Tânia; Gomes, Ana L; Zhu, Zhenping; Wu, Yan; Dias, Sérgio

2011-01-05

161

Cancer stem cells: lessons from leukemia  

Microsoft Academic Search

A fundamental problem in cancer research is identifi- cation of the cell type capable of initiating and sustaining growth of the tumor - the cancer stem cell (CSC). While the existence of CSCs was first proposed over 40 years ago, only in the past decade have these cells been identified and characterized in hematological malignancies. Recent studies have now described

Jean C. Y. Wang; John E. Dick

2005-01-01

162

Advances in hematopoietic stem cell transplantation in chronic myeloid leukemia.  

PubMed

Treatment of chronic myeloid leukemia (CML) has evolved dramatically with the development of tyrosine kinase inhibitors (TKIs). This past decade also witnessed major advances in the field of allogeneic hematopoietic stem cell transplantation (alloHSCT) that led to better patients' outcomes. Progress in the exploitation of alternative sources of stem cells, development of novel conditioning regimens, discovery of innovative graft-versus-host prophylactic strategies, and advances in supportive care as well as positioning of alloHSCT in the overall management of CML are discussed in this article. PMID:24099673

Veldman, Rachel; El Rassi, Fuad; Holloway, Stacie; Langston, Amelia; Khoury, Hanna Jean

2013-10-01

163

Ultrastructure of adult T-cell leukemia\\/lymphoma  

Microsoft Academic Search

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

Tadaaki Eimoto; Tetsuji Mitsui; Masahiro Kikuchi

1981-01-01

164

Adult T-cell leukemia/lymphoma triggered by adalimumab.  

PubMed

Here, we describe a 48-year-old woman infected by the human T-cell lymphotropic virus type 1 (HTLV-1) with spondyloarthritis, uveitis, bilateral episcleritis and neurogenic bladder. She had a history of a probable infective dermatitis associated with HTLV-1 (IDH) in childhood. After the use of adalimumab, she developed lymphocytosis and a cutaneous lymphoma associated with IDH. She had the diagnoses of IDH and of chronic adult T-cell leukemia/lymphoma, supported by the demonstration of proviral integration in the cutaneous lesion. PMID:23911677

Bittencourt, Achilea L; Oliveira, Pedro D; Bittencourt, Valeria G; Carvalho, Edgar M; Farre, Lourdes

2013-08-01

165

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

SciTech Connect

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.

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

1980-10-03

166

Bioactive Actions of Pomegranate Fruit Extracts on Leukemia Cell Lines In Vitro Hold Promise for New Therapeutic Agents for Leukemia  

Microsoft Academic Search

Studies suggest that pomegranates contain bioactive chemicals with potential for treatment and prevention of cancer. Pomegranate juice extracts (PJE) have been shown to inhibit cellular proliferation and tumor growth and induce cell death via apoptosis in a number of cancer cell lines. However, to date, few studies have investigated the potential of PJE in the treatment of leukemia. We investigated

Haytham Dahlawi; Nicola Jordan-Mahy; Malcolm R. Clench; Christine L. Le Maitre

2011-01-01

167

Bioactive Actions of Pomegranate Fruit Extracts on Leukemia Cell Lines In Vitro Hold Promise for New Therapeutic Agents for Leukemia  

Microsoft Academic Search

Studies suggest that pomegranates contain bioactive chemicals with potential for treatment and prevention of cancer. Pomegranate juice extracts (PJE) have been shown to inhibit cellular proliferation and tumor growth and induce cell death via apoptosis in a number of cancer cell lines. However, to date, few studies have investigated the potential of PJE in the treatment of leukemia. We investigated

Haytham Dahlawi; Nicola Jordan-Mahy; Malcolm R. Clench; Christine L. Le Maitre

2012-01-01

168

T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias  

PubMed Central

Large granular lymphocyte (LGL) leukemia is a rare disorder of cytotoxic lymphocytes. LGL cells play an integral role in the immune system and are divided into two major lineages of CD3? natural killer (NK) cells and CD3+ T cells that circulate throughout the blood in search of infected cells, in which they will make contact through a receptor ligand and induce cell death. LGLs cells are also programmed to undergo apoptosis after contact with an infected target cell; however they continue to survive in individuals with LGL leukemia. This unchecked proliferation and cytotoxicity of LGLs in patients results in autoimmunity or malignancy. Rheumatoid arthritis is the most common autoimmune condition seen in individuals with LGL leukemia; however, LGL leukemia is associated with a wide spectrum of other autoimmune diseases. Patients may also suffer from other hematological conditions including hemolytic anemia, pure red cell aplasia, and neutropenia which lead to recurrent bacterial infections. Currently, the only established treatment involves a low dose of an immunosuppressive regimen with methotrexate, in which 40–50% of patients are either resistant or do not respond. In order to establish new therapeutics it is important to understand the current state of LGL leukemia both in clinic and in basic research.

Watters, Rebecca J.; Liu, Xin; Loughran, Thomas P.

2013-01-01

169

Hairy black holes, horizon mass and solitons  

Microsoft Academic Search

Properties of the horizon mass of hairy black holes are discussed with emphasis on certain subtle and initially unexpected features. A key property suggests that hairy black holes may be regarded as `bound states' of ordinary black holes (without hair) and coloured solitons. This model is then used to predict the qualitative behaviour of the horizon properties of hairy black

Abhay Ashtekar; Alejandro Corichi; Daniel Sudarsky

2001-01-01

170

Method for differential diagnosis of T cell leukemias using monoclonal antibodies  

SciTech Connect

This patent describes monoclonal antibody 3-3 (HB8369) and 3-40 (HB8368) not capable of immunological reaction with normal, human peripheral T or B blood cell antigens, normal human thymocyte antigens or normal, human bone marrow precursor cell antigens but capable of immunological reaction with separate and distinct T-ALL leukemia antigens (T-ALL) having molecular weights of approximately 35-40,000 KD. The monoclonal antibodies are capable of distinguishing T-ALL leukemia from cutaneous T-cell lymphoma (CTCL), adult T cell leukemia (ATL) and T-cell chronic lymphocytic leukemia (T-CLL) and are further capable of subsetting T-ALL leukemia into E-Rosette positive and E-Rosette negative cells.

Knowles, R.W.; Dupont, B.; Naito, K.; Morishima, Y.

1987-02-24

171

Ovarian Reserve in Women Treated for Acute Lymphocytic Leukemia or Acute Myeloid Leukemia with Chemotherapy, but Not Stem Cell Transplantation  

PubMed Central

Purpose. It is well known that chemotherapy regimens may have a negative effect on ovarian reserve, leading to amenorrhea or premature ovarian failure. There are little data regarding the effects of leukemia chemotherapy on ovarian reserve, specifically in women who received the chemotherapy as adults and are having regular menstrual periods. Our primary objective was to determine if premenopausal women with a history of chemotherapy for leukemia, without subsequent stem cell transplantation, have decreased ovarian reserve. Materials and Methods. We measured ovarian reserve in five women who had been treated for acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) and compared them to age-matched control women without a history of chemotherapy. Results. There appeared to be a trend towards lower antimullerian hormone and antral follicle counts and higher follicle-stimulating hormone levels in the leukemia group. Conclusion. Our results indicate that chemotherapy for AML or ALL without stem cell transplantation may compromise ovarian reserve. Although our results should be confirmed by a larger study, oncologists, infertility specialists, and patients should be aware of the potential risks to ovarian function and should be counseled on options for fertility preservation.

Rossi, Brooke V.; Missmer, Stacey; Correia, Katharine F.; Wadleigh, Martha; Ginsburg, Elizabeth S.

2012-01-01

172

Autologous hematopoietic stem cell transplantation as salvage treatment for advanced B cell chronic lymphocytic leukemia  

Microsoft Academic Search

Given the generally poor outcome of advanced B cell chronic lymphocytic leukemia, experimental approaches are warranted, especially for younger patients in whom classical treatments have failed. We therefore conducted a prospective single-center study, using polychemotherapy (ESHAP) to prepare patients for hematopoietic stem cell collection and autologous stem cell transplantation as consolidation therapy. Twenty patients entered the study. An adequate response

L Sutton; K Maloum; H Gonzalez; H Zouabi; N Azar; C Boccaccio; F Charlotte; J-M Cosset; J Gabarre; V Leblond; H Merle-Beral; J-L Binet

1998-01-01

173

Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells  

Microsoft Academic Search

We analyzed the expression of cell surface antigens and granulocyte colony-stimulating factor (G-CSF) receptors using flow\\u000a cytometry, the expression of G-CSF mRNA receptor, using reverse transcription (RT)-PCR, and tested the effect of G-CSF on\\u000a leukemia colony formation. A total of 14 lymphocytic leukemia patients were examined, seven with acute lymphocytic leukemia\\u000a (ALL), two with adult T-cell leukemia (ATL), two with

A. Handa; T. Kashimura; S. Takeuchi; A. Yamamoto; I. Murohashi; M. Bessho; K. Hirashima

2000-01-01

174

Effect of Thimerosal in Leukemia, in Leukemic Cell Lines, and on Normal Hematopoyesis1  

Microsoft Academic Search

Anti-thymocyte globulin (ATG), a horse antiserum to human thymus tissue, has been shown to induce granulocytic differentiation of the III- 60 human leukemia cell line. In this paper we describe the effect of ATG on leukemic blasts and its effect on other human leukemia cell lines in vitro. The in vitro differentiation effect of ATG was observed in blasts from

Timothy J. Panella; Andrew T. Huang

175

Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition  

Microsoft Academic Search

PURPOSE: Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL might in fact represent second leukemias. PATIENTS AND METHODS: In 22 patients with T-ALL who had late relapses

T. Szczepanski; V. H. van der Velden; E. Waanders; R. P. Kuiper; P. Van Vlierberghe; B. Gruhn; C. Eckert; R. Panzer-Grumayer; G. Basso; H. Cave; U. Z. Stadt; D. Campana; A. Schrauder; R. Sutton; E. van Wering; J. P. P. Meijerink; J. J. van Dongen

2011-01-01

176

Hematopoietic stem cell transplantation for patients with chronic myeloid leukemia  

Microsoft Academic Search

Objective  To evaluate the effects of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for patients with chronic\\u000a myeloid leukemia(CML).\\u000a \\u000a \\u000a \\u000a Methods  Fifty-seven patients with CML were treated by HSCT, including 8 cases treated with autologous transplantation purged in vivo\\u000a and in vitro of minimal residual disease (MRD), 39 cases with related donor allogeneic HSCT (allo-HSCT) and 10 cases with\\u000a unrelated donor allo-HSCT.

Qifa Liu; Zhiping Fan; Jing Sun; Yu Zhang; Xiaoli Liu; Dan Xu; Bing Xu; Ru Feng; Fanyi Meng; Shuyun Zhou

2004-01-01

177

Plasma cell leukemia: case series from a tertiary center with review of literature.  

PubMed

Plasma cell leukemia is an unusual manifestation of multiple myeloma, reported to occur in 2% of newly diagnosed patients. It may either present at the time of diagnosis (primary) or evolve as a late feature in the course of multiple myeloma (secondary). Most clinical signs of myeloma are observed in plasma cell leukemia, although osteolytic lesions and bone pain are less frequent and lymphadenopathy, organomegaly and renal failure are more often present. The immunophenotype of plasma cell leukemia differs typically from that of myeloma by lack of aberrant CD56 expression. An abnormal karyotype is more frequently found in plasma cell leukemia and there is higher incidence of unfavourable cytogenetics. Plasma cell leukemia is an aggressive disease, characterized by a fulminant course and a short survival. We are reporting cases of this rare condition which presented at our center over 3 years along with review of literature. PMID:23449039

Naseem, Shano; Kaur, Sukhpreet; Gupta, Ritu; Kashyap, Rajesh; Nityanand, Soniya

2011-07-21

178

Ganglioside GM3 Can Induce Megakaryocytoid Differentiation of Human Leukemia Cell Line K562 Cells1  

Microsoft Academic Search

The role of acidic glycosphingolipids in cell growth and differentiation was investigated using the multipotent leukemia cell line KS62. When (¡Miwas added to cell culture media, the growth of K562 cells was remarkably inhibited and the cells were shown to have megakaryocytoid morphology. Ultrastructural study demonstrated that KS62 cells treated with CM., had platelet peroxidase-positive structures, which were con sidered

Mitsuru Nakamura; Keita Kirito; Jinko Yamanoi; Tasuku Wainai; Hisao Nojiri; Masaki Saito

1991-01-01

179

Hand mirror cell leukemia--immunologic and ultrastructural studies.  

PubMed

Acute lymphoblastic leukemia (ALL) with hand mirror cell (HMC) variant was diagnosed in a 26-year-old black man in May 1978. Hemoglobin was 3.6 g/dl; the platelet count was 19.0 x 10(9)/l; leukocyte count was 8.4 x 10(9)/l with 40% blasts, 66% of which had HMC appearance. Cytochemical studies, terminal deoxynucleotidyl transferase level, and immunologic marker studies indicated a non-T/non-B lymphoblastic origin of the leukemic population. Electron microscopic studies confirmed the hand mirror appearance. Mitochondria were more numerous in these cells compared with other lymphoid cells. Cytogenetic studies showed a 46XY karyotype. Our studies confirmed the previous studies reported by Stass, et al of lymphoblastic origin of HMC leukemia. The patient responded to treatment with vincristine, prednisone and L-asparaginase and went into complete remission. It appears that this morphologic variant of ALL does exist and is not an artifact. PMID:6939474

Shah-Reddy, I; Mirchandani, I; Bishop, C R

1981-02-15

180

Viscous flow on hairy surfaces  

NASA Astrophysics Data System (ADS)

Viscous flow on a hairy surface is investigated analytically. This flow can be the viscous sublayer of a turbulent boundary layer. The hairy surface is modeled with strings stretched in the streamwise direction above a plate. Velocity and shear stress distributions are calculated. As a by-product, the theory provides orthogonal grids which may be utilized in future numerical flow computations. The distance of the apparent origin of the velocity profile from the surface is determined. This distance characterizes how deep the strings protrude into the flow. It is found that thin strings protrude much deeper into the flow than normal riblets do. For the latter, drag reduction has been shown experimentally.

Bartenwerfer, M.; Bechert, D. W.

1991-02-01

181

Clinical Relevance of Survivin as a Biomarker in Neoplasms, Especially in Adult T-Cell Leukemias and Acute Leukemias  

Microsoft Academic Search

Survivin has been identified as one of the top 4 transcripts among 3.5 million human transcriptomes uniformly upregulated\\u000a in cancer tissues but not in normal tissues. Therefore, we quantitatively determined the messenger RNA (mRNA) expression profile\\u000a for survivin by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 113 patients with leukemias,\\u000a such as adult T-cell leukemia (ATL), acute lymphoid

Kazuyuki Sugahara; Akiko Uemura; Hitomi Harasawa; Hiroshi Nagai; Yoichi Hirakata; Masao Tomonaga; Kenn Murata; Hiroshi Sohda; Toru Nakagoe; Sin-ichi Shibasaki; Yasuaki Yamada; Shimeru Kamihira

2004-01-01

182

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells  

PubMed Central

Background. Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. Methods. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF–secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. Results. At a median follow-up of 2.9 (range, 1–4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%–94%) and 88% (95% CI, 59%–97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-?, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%–33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Conclusion. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Trial registration. Clinicaltrials.gov NCT00442130. Funding. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Burkhardt, Ute E.; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R.; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T.; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L.; Brusic, Ana; McDonough, Sean M.; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R.; Canning, Christine M.; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H.; Mulligan, Richard C.; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J.; Dranoff, Glenn; Alyea, Edwin P.; Wu, Catherine J.

2013-01-01

183

Ecotropic murine leukemia virus-induced fusion of murine cells.  

PubMed Central

Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with [3H]thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells. Images

Pinter, A; Chen, T E; Lowy, A; Cortez, N G; Silagi, S

1986-01-01

184

Ecotropic murine leukemia virus-induced fusion of murine cells  

SciTech Connect

Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with (/sup 3/H)thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells.

Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

1986-03-01

185

Donor cell leukemia after allogeneic peripheral blood stem cell transplantation: a case report and literature review  

Microsoft Academic Search

A 49-year-old male developed recurrent acute myeloid leukemia 27 months after allogeneic peripheral blood stem cell transplantation\\u000a (PBSCT) from an HLA-identical brother. The immunophenotype of the blastic cell population was incompatible with that of the\\u000a pre-transplant blast cells; a mutation in C\\/EBPA gene was found in the pre-transplant blast cells that was not present in the post-transplant blast cells, and short

Makoto Murata; Yuichi Ishikawa; Haruhiko Ohashi; Seitaro Terakura; Kazutaka Ozeki; Hitoshi Kiyoi; Tomoki Naoe

2008-01-01

186

Prodigiosin induces apoptosis of B and T cells from B-cell chronic lymphocytic leukemia.  

PubMed

We have previously reported that prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosene) induces apoptosis in human hematopoietic cancer cell lines with no marked toxicity in nonmalignant cell lines. In this study, we demonstrate that prodigiosin induces apoptosis of B-cell chronic lymphocytic leukemia (B-CLL) cells (n=32 patients). The dose-response for the cytotoxic effect of prodigiosin was analyzed in cells from 12 patients showing an IC(50) of 116+/-25 nM. Prodigiosin induced apoptosis of B-CLL cells through caspase activation. We also analyzed the cytotoxic effect of prodigiosin in T cells from B-CLL samples and no differences were observed with respect to leukemia cells. This is the first report showing that prodigiosin induces apoptosis in human primary cancer cells. PMID:12682632

Campàs, C; Dalmau, M; Montaner, B; Barragán, M; Bellosillo, B; Colomer, D; Pons, G; Pérez-Tomás, R; Gil, J

2003-04-01

187

Cell fusion induced by the murine leukemia virus envelope glycoprotein.  

PubMed Central

To determine whether ecotropic murine leukemia virus (MuLV) envelope glycoproteins are sufficient to cause cell-to-cell fusion when expressed in the absence of virus production, we used an ecotropic MuLV, AKV, to construct env expression vectors that lack the gag and pol genes. The rat cell line XC, which undergoes cell-to-cell fusion upon infection with ecotropic MuLV, was transfected with wild-type env expression vectors, and high levels of syncytium formation resulted. Transfection of the murine cell line NIH 3T3 with expression vectors containing the wild-type or mutated env region did not result in syncytium formation. Immunoprecipitation analysis of the envelope glycoproteins expressed in NIH 3T3 and XC cells showed that the mature surface glycoprotein expressed in XC cells was of a much lower apparent molecular weight than that expressed in NIH 3T3 cells. Further characterization showed that most if not all of this difference was the result of differences in glycosylation. Finally, site-directed mutagenesis was used to introduce several conservative and nonconservative changes into the amino-terminal region of the transmembrane protein. Analysis of the effect of these mutations confirmed that this region is a fusion domain. Images

Jones, J S; Risser, R

1993-01-01

188

Ex vivo methods for targeting or depleting acute myeloid leukemia cancer stem cells  

US Patent & Trademark Office Database

Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets.

Majeti; Ravindra (Stanford, CA); Weissman; Irving L. (Stanford, CA)

2013-01-29

189

Properties of Leukemia Stem Cells in a Novel Model of CML Progression to Lymphoid Blast Crisis.  

National Technical Information Service (NTIS)

The objective of the study was to employ a novel mouse model of CML blast crisis to characterize various forms of leukemia stem cells (LSC) and their relative properties. In particular, distinguishing how differing normal target cells contribute to diseas...

C. T. Jordan

2007-01-01

190

Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells  

SciTech Connect

The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I-CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives.

Faguet, G.B.; Agee, J.F.; DiPiro, J.T. (Veterans Administration Medical Center, Augusta, GA (USA))

1990-05-01

191

Natural Antibodies to Human Retrovirus HTLV in a Cluster of Japanese Patients with Adult T Cell Leukemia  

Microsoft Academic Search

Human T cell lymphoma leukemia virus (HTLV) is a human retrovirus (RNA tumor virus) that was originally isolated from a few patients with leukemias or lymphomas involving mature T lymphocytes. Here we report that the serum of Japanese patients with adult T cell leukemia, but not the serum of tested normal donors, contains high titers of antibodies to HTLV. These

Marjorie Robert-Guroff; Yoshinobu Nakao; Kunihiro Notake; Yohei Ito; Ann Sliski; Robert C. Gallo

1982-01-01

192

Force Microscopy of Nonadherent Cells: A Comparison of Leukemia Cell Deformability  

PubMed Central

Atomic force microscopy (AFM) has become an important tool for quantifying mechanical properties of biological materials ranging from single molecules to cells and tissues. Current AFM techniques for measuring elastic and viscoelastic properties of whole cells are based on indentation of cells firmly adhered to a substrate, but these techniques are not appropriate for probing nonadherent cells, such as passive human leukocytes, due to a lateral instability of the cells under load. Here we present a method for characterizing nonadherent cells with AFM by mechanically immobilizing them in microfabricated wells. We apply this technique to compare the deformability of human myeloid and lymphoid leukemia cells and neutrophils at low deformation rates, and we find that the cells are well described by an elastic model based on Hertzian mechanics. Myeloid (HL60) cells were measured to be a factor of 18 times stiffer than lymphoid (Jurkat) cells and six times stiffer than human neutrophils on average (E? = 855 ± 670 Pa for HL60 cells, E? = 48 ± 35 Pa for Jurkat cells, E? = 156 ± 87 for neutrophils, mean ± SD). This work demonstrates a simple method for extending AFM mechanical property measurements to nonadherent cells and characterizes properties of human leukemia cells that may contribute to leukostasis, a complication associated with acute leukemia.

Rosenbluth, Michael J.; Lam, Wilbur A.; Fletcher, Daniel A.

2006-01-01

193

Isolation of Human T-Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS)  

Microsoft Academic Search

Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral

Robert C. Gallo; Prem S. Sarin; E. P. Gelmann; Marjorie Robert-Guroff; Ersell Richardson; V. S. Kalyanaraman; Dean Mann; Gurdip D. Sidhu; Rosalyn E. Stahl; Susan Zolla-Pazner; Jacque Leibowitch; Mikulas Popovic

1983-01-01

194

Association of Oxidative Stress with Realgar-Induced Differentiation in Human Leukemia HL60 Cells  

Microsoft Academic Search

Background: Realgar (arsenic sulfide, As4S4) has been shown to have clinical efficacy in patients with newly diagnosed and relapsed acute promyelocytic leukemia. Mechanistic studies have demonstrated that realgar is able to induce cell differentiation. Methods: The oxidative stress in the realgar-induced differentiation was examined with human leukemia HL-60 cells. Cell differentiation was evaluated by the expression of cell surface antigen

Li-Wen Wang; Yan-Ling Shi; Nan Wang; Bao-Di Gou; Tian-Lan Zhang; Kui Wang

2009-01-01

195

Notch2 inhibits proliferation of chronic myeloid leukemia cells.  

PubMed

The Notch signaling pathway has been shown to be involved in the progression of chronic myeloid leukemia (CML). The aim of this study was to investigate the effects of exogenous Notch2 overexpression on cell proliferation and possible mechanisms in the human CML cell line K562. When exogenous intracellular fragment of Notch2 (ICN2) was transfected into K562 cells with Lipofectamine™ 2000, the expression of Notch2 mRNA and protein were upregulated. Cell numbers decreased and the proliferation was inhibited significantly after transfection with ICN2. G1 phase cells increased and S phase cells decreased 48 h after transfection. Finally, the expression of Numb, Bcl-2, NF-?B and TGF-?1 was detected. It was found that the expression of NF-?B and TGF-?1 mRNA was increased, while Bcl-2 was downregulated, with Numb expression unchanged. Our study indicates that the Notch pathway is activated in K562 cells after ICN2 transfection. It inhibited the proliferation of K562 cells, likely by upregulating the expression of NF-?B and TGF-?1 mRNA and downregulating the expression of Bcl-2. PMID:23599800

Yang, Zesong; Yang, Chunxiu; Zhang, Shunjun; Li, Ying; Chen, Jianbin

2013-01-29

196

Leydig cell damage after testicular irradiation for lymphoblastic leukemia  

SciTech Connect

The effect of testicular irradiation on Leydig cell function has been studied in a group of boys irradiated between 1 and 5 years earlier for a testicular relapse of acute lymphoblastic leukemia. Six of the seven boys irradiated during prepubertal life had an absent testosterone response to HCG stimulation. Two of the four boys irradiated during puberty had an appropriate basal testosterone level, but the testosterone response to HCG stimulation was subnormal in three of the four. Abnormalities in gonadotropin secretion consistent with testicular damage were noted in nine of the 11 boys. Evidence of severe Leydig cell damage was present irrespective of whether the boys were studied within 1 year or between 3 and 5 years after irradiation, suggesting that recovery is unlikely. Androgen replacement therapy has been started in four boys and will be required by the majority of the remainder to undergo normal pubertal development.

Shalet, S.M.; Horner, A.; Ahmed, S.R.; Morris-Jones, P.H.

1985-01-01

197

Lymphokine Production by Cultured Human T Cells Transformed by Human T-Cell Leukemia-Lymphoma Virus-I  

Microsoft Academic Search

Cell-free conditioned media from human T cells transformed by human T-cell leukemia-lymphoma virus (HTLV-I) were tested for the production of soluble biologically active factors, including several known lymphokines. The cell lines used were established from patients with T-cell leukemia-lymphoma and from human umbilical cord blood and bone marrow leukocytes transformed by HTLV-I in vitro. All of the cell lines liberated

S. Z. Salahuddin; P. D. Markham; S. G. Lindner; J. Gootenberg; M. Popovic; H. Hemmi; P. S. Sarin; R. C. Gallo

1984-01-01

198

Regulation of myeloid leukemia by the cell fate determinant Musashi  

PubMed Central

Chronic myelogenous leukemia (CML) can progress from an indolent chronic phase to an aggressive blast crisis phase1 but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML2,3 to show that disease progression is regulated by the Musashi-Numb signaling axis4,5. Specifically, we find that chronic phase is marked by high and blast crisis phase by low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced phase disease in vivo. As a possible explanation for the decreased levels of Numb in blast crisis, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML6,7, can trigger expression of the RNA binding protein Musashi2 (Msi2) which in turn represses Numb. Importantly, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally, we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for therapy of aggressive leukemias.

Ito, Takahiro; Kwon, Hyog Young; Zimdahl, Bryan; Congdon, Kendra L.; Blum, Jordan; Lento, William E.; Zhao, Chen; Lagoo, Anand; Gerrard, Gareth; Foroni, Letizia; Goldman, John; Goh, Harriet; Kim, Soo-Hyun; Kim, Dong-Wook; Chuah, Charles; Oehler, Vivian G.; Radich, Jerald P.; Jordan, Craig T.; Reya, Tannishtha

2010-01-01

199

mTORC1 is essential for leukemia propagation but not stem cell self-renewal  

PubMed Central

Although dysregulation of mTOR complex 1 (mTORC1) promotes leukemogenesis, how mTORC1 affects established leukemia is unclear. We investigated the role of mTORC1 in mouse hematopoiesis using a mouse model of conditional deletion of Raptor, an essential component of mTORC1. Raptor deficiency impaired granulocyte and B cell development but did not alter survival or proliferation of hematopoietic progenitor cells. In a mouse model of acute myeloid leukemia (AML), Raptor deficiency significantly suppressed leukemia progression by causing apoptosis of differentiated, but not undifferentiated, leukemia cells. mTORC1 did not control cell cycle or cell growth in undifferentiated AML cells in vivo. Transplantation of Raptor-deficient undifferentiated AML cells in a limiting dilution revealed that mTORC1 is essential for leukemia initiation. Strikingly, a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity. We further demonstrated that the reactivation of mTORC1 in those cells restored their leukemia-initiating capacity. Thus, AML cells lacking mTORC1 activity can self-renew as AML stem cells. Our findings provide mechanistic insight into how residual tumor cells circumvent anticancer therapies and drive tumor recurrence.

Hoshii, Takayuki; Tadokoro, Yuko; Naka, Kazuhito; Ooshio, Takako; Muraguchi, Teruyuki; Sugiyama, Naoyuki; Soga, Tomoyoshi; Araki, Kimi; Yamamura, Ken-ichi; Hirao, Atsushi

2012-01-01

200

Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models  

SciTech Connect

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.

Hara, H.; Seon, B.K.

1987-05-01

201

Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia  

PubMed Central

NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that Mcl-1 was overexpressed in leukemic NK cells and that knockdown of Mcl-1 induced apoptosis in these leukemic cells. In vitro treatment of human and rat NK leukemia cells with FTY720 led to caspase-dependent apoptosis and decreased Mcl-1 expression in a time- and-dose-dependent manner. These biologic effects could be inhibited by blockade of reactive oxygen species generation and the lysosomal degradation pathway. Lipidomic analyses after FTY720 treatment demonstrated elevated levels of sphingosine, which mediated apoptosis of leukemic NK cells in vitro. Importantly, systemic administration of FTY720 induced complete remission in the syngeneic Fischer rat model of NK-cell leukemia. Therapeutic efficacy was associated with decreased expression of Mcl-1 in vivo. These data demonstrate that therapeutic benefit of FTY720 may result from both altered sphingolipid metabolism as well as enhanced degradation of a key component of survival signaling.

Liao, Aijun; Broeg, Kathleen; Fox, Todd; Tan, Su-Fern; Watters, Rebecca; Shah, Mithun Vinod; Zhang, Lucy Q.; Li, Yongping; Ryland, Lindsay; Yang, Jun; Aliaga, Cesar; Dewey, Alden; Rogers, Andrew; Loughran, Kelly; Hirsch, Leah; Jarbadan, Nancy Ruth; Baab, Kendall Thomas; Liao, Jason; Wang, Hong-Gang; Kester, Mark; Desai, Dhimant; Amin, Shantu; Loughran, Thomas P.

2011-01-01

202

Cell Cycle-Specific Function of Ikaros in Human Leukemia  

PubMed Central

Background The loss of Ikaros is associated with the development of B and T cell leukemia. Data on Ikaros function, including its role as a tumor suppressor and a regulator of cell cycle progression, come almost exclusively from murine studies; little is known of the mechanisms that regulate human Ikaros function. Our studies are the first to examine the function and regulation of human Ikaros isoforms during the cell cycle in human ALL. Procedures Electromobility shift assay (EMSA), confocal microscopy, and phosphopeptide mapping were used to study Ikaros function during different stages of the cell cycle. Results The DNA-binding activity of human Ikaros complexes undergoes dynamic changes as the cell cycle progresses. In S phase, Ikaros DNA-binding affinity for regulatory regions of its target genes decreases, while its binding to pericentromeric heterochromatin is preserved and correlates with Ikaros pericentromeric localization. These S phase-specific changes in Ikaros function are controlled by phosphorylation via the CK2 kinase pathway. During cell cycle progression, the subcellular pericentromeric localization of the largest human Ikaros isoforms is different from that in mouse cells, suggesting unique functions for human Ikaros. Conclusions Our results demonstrate that the function of Ikaros is cell cycle-specific and controlled by CK2-mediated phosphorylation during S phase of the cell cycle in human T-cell and B-cell ALL. The differences we observe in murine and human Ikaros function highlight the importance of using human cells in studies of ALL. These data identify the CK2 pathway as a target for therapies in ALL.

Li, Zhanjun; Song, Chunhua; Ouyang, Hongsheng; Lai, Liangxue; Payne, Kimberly J.; Dovat, Sinisa

2011-01-01

203

Serotonin-like immunoreactivity in Merkel cells and their afferent neurons in touch domes from the hairy skin of rats.  

PubMed

Immunoreactivity to serotonin was observed in Merkel cells as well as the afferent type I nerves terminating upon them in touch domes excised from the belly skin of rats. Type I nerves were strongly immunoreactive and could be traced through the dermis of the domal papilla. Merkel cell immunoreactivity was sometimes seen in the entire cell, but was often localized in the Merkel cell cytoplasm adjacent to nerve terminals and may have been in the terminals themselves. Domes were fixed by immersion in 4% paraformaldehyde-lysine-sodium-m-periodate (PLP) fixative at 4 degrees C for 2.5-3 hours and cryoprotected in 30% sucrose overnight. Sections were processed with the avidin-biotin complex peroxidase (ABC), peroxidase-antiperoxidase (PAP), and indirect immunofluorescence techniques with rabbit antiserum generated against serotonin. PMID:1536455

English, K B; Wang, Z Z; Stayner, N; Stensaas, L J; Martin, H; Tuckett, R P

1992-01-01

204

Modulation of innate immune responses during human T-cell leukemia virus (HTLV1) pathogenesis  

Microsoft Academic Search

Infection with the Human T-cell Leukemia virus type I (HTLV-1) retrovirus results in a number of diverse pathologies, including the aggressive, fatal T-cell malignancy adult T-cell leukemia (ATL) and the chronic, progressive neurologic disorder termed HTLV-1-associated myelopathy\\/tropical spastic paraparesis (HAM\\/TSP). Worldwide, it is estimated there are 15–20 million HTLV-1-infected individuals; although the majority of HTLV-1-infected individuals remain asymptomatic carriers (AC)

Stéphanie Olière; Renée Douville; Alexandre Sze; S. Mehdi Belgnaoui; John Hiscott

205

Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling  

Microsoft Academic Search

Human T-cell leukemia virus type-1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and neurological syn- dromes. HTLV-1 encodes the oncoprotein Tax-1, which modulates viral and cellular gene expression leading to T-cell transfor- mation. Guanine nucleotide-binding pro- teins (G proteins) and G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins known and are involved in the regulation of

Jean-Claude Twizere; Jean-Yves Springael; Mathieu Boxus; Arsene Burny; Franck Dequiedt; Jean-Francois Dewulf; Julie Duchateau; Daniel Portetelle; Patrice Urbain; Carine Van Lint; Patrick L. Green; Renaud Mahieux; Marc Parmentier; Luc Willems; Richard Kettmann

2007-01-01

206

Anti-adult T-cell leukemia\\/lymphoma effects of indole-3-carbinol  

Microsoft Academic Search

BACKGROUND: Adult T-cell leukemia\\/lymphoma (ATLL) is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1), and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C), a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic,

Yoshiaki Machijima; Chie Ishikawa; Shigeki Sawada; Taeko Okudaira; Jun-nosuke Uchihara; Yuetsu Tanaka; Naoya Taira; Naoki Mori

2009-01-01

207

Human T-Cell Leukemia Virus Type I at Age 25: A Progress Report  

Microsoft Academic Search

It has been 25 years since the discovery of human T-cell leukemia virus type I (HTLV-I) and its role in adult T-cell leukemia. Here, in brief, we review the current state of our understanding of HTLV-I epidemiology, viral biology, patho- genesis, and treatment. We discuss how HTLV-I may transform cells through destabilization of cellular genomic integrity and induction of cellular

Masao Matsuoka; Kuan-Teh Jeang

208

Expression of c-myc is not critical for cell proliferation in established human leukemia lines  

Microsoft Academic Search

BACKGROUND: A study was undertaken to resolve preliminary conflicting results on the proliferation of leukemia cells observed with different c-myc antisense oligonucleotides. RESULTS: RNase H-active, chimeric methylphosphonodiester \\/ phosphodiester antisense oligodeoxynucleotides targeting bases 1147–1166 of c-myc mRNA downregulated c-Myc protein and induced apoptosis and cell cycle arrest respectively in cultures of MOLT-4 and KYO1 human leukemia cells. In contrast, an

David M Tidd; Richard V Giles; Caroline M Broughton; Richard E Clark

2001-01-01

209

Secondary Acute Monocytic Leukemia Occurring during the Treatment of a Testicular Germ Cell Tumor  

Microsoft Academic Search

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors is a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of acute monocytic leukemia occurring in a 44-year-old man who received etoposide-based chemotherapy and radiotherapy for a recurrent, metastatic testicular germ cell tumor. The patient recevied 14 cycles of systemic

Norio Nonomura; Nobukazu Murosaki; Yasuyuki Kojima; Nobuyuki Kondoh; Toshinobu Seguchi; Yoshito Takeda; Yusuke Oji; Hiroyasu Ogawa; Haruo Sugiyama; Tsuneharu Miki; Äkïhïko Okuyama

1997-01-01

210

Ayanin diacetate-induced cell death is amplified by TRAIL in human leukemia cells.  

PubMed

Here we demonstrate that the semi-synthetic flavonoid ayanin diacetate induces cell death selectively in leukemia cells without affecting the proliferation of normal lymphocytes. Incubation of human leukemia cells with ayanin diacetate induced G(2)-M phase cell cycle arrest and apoptosis which was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the overexpression of Bcl-x(L). Ayanin diacetate-induced cell death was found to be associated with: (i) loss of inner mitochondrial membrane potential, (ii) the release of cytochrome c, (iii) the activation of multiple caspases, (iv) cleavage of poly(ADP-ribose) polymerase and (v) the up-regulation of death receptors for TRAIL, DR4 and DR5. Moreover, the combined treatment with ayanin diacetate and TRAIL amplified cell death, compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer. PMID:23063980

Marrero, María Teresa; Estévez, Sara; Negrín, Gledy; Quintana, José; López, Mariana; Pérez, Francisco J; Triana, Jorge; León, Francisco; Estévez, Francisco

2012-10-11

211

The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo  

PubMed Central

Therapeutic options for advanced B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are limited. Available treatments can also deplete T lymphocytes, leaving patients at risk of life-threatening infections. In the National Cancer Institute cell line screen, the structurally unique natural product silvestrol produces an unusual pattern of cytotoxicity that suggests activity in leukemia and selectivity for B cells. We investigated silvestrol efficacy using primary human B-leukemia cells, established B-leukemia cell lines, and animal models. In CLL cells, silvestrol LC50 (concentration lethal to 50%) is 6.9 nM at 72 hours. At this concentration, there is no difference in sensitivity of cells from patients with or without the del(17p13.1) abnormality. In isolated cells and whole blood, silvestrol is more cytotoxic toward B cells than T cells. Silvestrol causes early reduction in Mcl-1 expression due to translational inhibition with subsequent mitochondrial damage, as evidenced by reactive oxygen species generation and membrane depolarization. In vivo, silvestrol causes significant B-cell reduction in E?-Tcl-1 transgenic mice and significantly extends survival of 697 xenograft severe combined immunodeficient (SCID) mice without discernible toxicity. These data indicate silvestrol has efficacy against B cells in vitro and in vivo and identify translational inhibition as a potential therapeutic target in B-cell leukemias.

Edwards, Ryan B.; Lozanski, Gerard; West, Derek A.; Shin, Jungook D.; Vargo, Melissa A.; Davis, Melanie E.; Rozewski, Darlene M.; Johnson, Amy J.; Su, Bao-Ning; Goettl, Virginia M.; Heerema, Nyla A.; Lin, Thomas S.; Lehman, Amy; Zhang, Xiaoli; Jarjoura, David; Newman, David J.; Byrd, John C.; Kinghorn, A. Douglas; Grever, Michael R.

2009-01-01

212

Differences in the Frequency of Normal and Clonal Precursors of Colony-Forming Cells in Chronic Myelogenous Leukemia and Acute Myelogenous Leukemia  

Microsoft Academic Search

Acute myelogenous leukemia (AML) is a clonal disease that is heterogeneous with respect to the pattern of differentiative expression of the leukemic progenitors. In some patients, the involved stem cells manifest pluripotent differentiative ex- pression, whereas in others, the involved progenitors mani- fest differentiative expression mainly restricted to the granu- locytic pathway. This is in contrast to chronic myelogenous leukemia

Irwin D. Bernstein; Jack W. Singer; Robert G. Andrews; David A. Flowers; Jerilyn Petersens; Laura Steinmann; Vesna Najfeld; David Savage; Steven Fruchtman; Zalmen Arlin; Philip J. Fialkow

1992-01-01

213

MZ3 induces apoptosis in human leukemia cells  

Microsoft Academic Search

Purpose  4-(4-Bromophenyl)-2,3-dihydro-N,3-bis(3,4,5-trimethoxyphenyl)-2-oxoidmi-dazole-1-carboxamide (MZ3) is one of the synthesized combretastatin-A-4 analogues\\u000a and has been reported that it displayed a promising specific activity against leukemia cell lines. Our purpose was to investigate\\u000a the mechanism of MZ3’s cytotoxicity.\\u000a \\u000a \\u000a \\u000a Methods  Cytotoxicity was measured by MTT method, apoptosis was measured by flow cytometry. DNA fragmentation was tested by agarose\\u000a gel electrophoresis. Mitochondrial membrane potential (??m) was detected

Liang Fang; Qiaojun He; Yongzhou Hu; Bo Yang

2007-01-01

214

Epigenetic regulation of cell signaling pathways in acute lymphoblastic leukemia.  

PubMed

Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer that is characterized by rapid and uncontrolled proliferation of immature B- or T-lymphoid precursors. Although ALL has been regarded as a genetic disease for many years, the crucial importance of epigenetic alterations in leukemogenesis has become increasingly evident. Epigenetic mechanisms, which include DNA methylation and histone modifications, are critical for gene regulation during many key biological processes. Here, we review the cell signaling pathways that are regulated by DNA methylation or histone modifications in ALL. Recent studies have highlighted the fundamental role of these modifications in ALL development, and suggested that future investigation into the specific genes and pathways that are altered by epigenetic mechanisms can contribute to the development of novel drug-based therapies for ALL. PMID:24059799

San Jose-Eneriz, Edurne; Agirre, Xabier; Rodríguez-Otero, Paula; Prosper, Felipe

2013-10-01

215

Discovery of B cell antigen on blast cells of patients with chronic myeloid leukemia  

Microsoft Academic Search

The presence of a common antigen on B lymphocytes of healthy blood donors and on myeloblasts of patients with chronic myeloid leukemia (CML) in the blast crisis (BC) stage was established with the aid of an antimyeloblast serum by the indirect surface immunofluorescence test. In the cytotoxic test this antigen was found on the blast cells of 27 patients with

L. F. Morozova; N. I. Belyanchikova; R. M. Radzikhovskaya; A. Yu. Baryshnikov; M. A. Volkova; Yu. É. Vinogradova; I. V. Frenovskaya; V. G. Markaryan; T. M. Polotskaya; E. R. Vasil'eva

1979-01-01

216

Putative tyrosine kinases expressed in K-562 human leukemia cells  

SciTech Connect

Tyrosine phosphorylation is important in the transmission of growth and differentiation signals; known tyrosine kinases include several oncoproteins and growth factor receptors. Interestingly, some differentiated cell types, such as erythrocytes and platelets contain high amounts of phosphotyrosine. The authors analyzed tyrosine kinases expressed in the K-562 chronic myelogenous leukemia cell line, which has a bipotential erythroid and megakaryoblastoid differentiation capacity. Analysis of 359 polymerase chain reaction-amplified cDNA clones led to the identification of 14 different tyrosine kinase-related sequences (JTK1-14). Two of the clones (JTK2 and JTK4) represent unusual members of the fibroblast growth factor receptor gene family, and the clones JTK5, JTK11, and JTK14 may also belong to the family of receptor tyrosine kinases but lack a close relationship to any known tyrosine kinase. Each of these different genes has its own characteristic expression pattern in K-562 cells and several other human tumor cell lines. In addition, the JTK11 and JTK14 mRNAs are induced during the megakaryoblastoid differentiation of K-562 cells. These tyrosine kinases may have a role in the differentiation of megakaryoblasts or in the physiology of platelets.

Partanen, J.; Maekelae, T.P.; Lehvaeslaiho, H.; Alitalo, K.; Alitalo, R. (Univ. of Helsinki (Finland))

1990-11-01

217

Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells  

Microsoft Academic Search

Mitochondrial damage with release of cytochrome c is implicated in cell death signalling pathways. To examine mitochondrial function in apoptotic cells, we applied high-resolution respirometry to human leukemia cells arrested in the G1- and S-phase by exposure to the glucocorticoid dexamethasone and nucleotide analogue gemcitabine. At 30% apoptosis, opposite effects were observed on respiratory capacity (71% and 131% of controls,

Kathrin Renner; Albert Amberger; Günther Konwalinka; Reinhard Kofler; Erich Gnaiger

2003-01-01

218

Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia  

Microsoft Academic Search

The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was

ZS Pavletic; ER Arrowsmith; PJ Bierman; SA Goodman; JM Vose; SR Tarantolo; RS Stein; G Bociek; JP Greer; CD Wu; JP Kollath; DD Weisenburger; A Kessinger; SN Wolff; JO Armitage

2000-01-01

219

Qualitative and quantitative characterization of Fas (CD95) expression and its role in primary human acute leukemia cells  

Microsoft Academic Search

Fas antigen, a cell surface molecule, directly mediates apoptosis, and is expressed on a limited number of human tissues. Blood or bone marrow samples from patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and mixed leukemia were examined qualitatively and quantitatively for the expression of Fas as well as its function using flow cytometry and the annexin V

Qian Li; Kazuto Tsuruda; Kazuyuki Sugahara; Natsuko Dateki; Etsuko Ohishi; Yasuaki Yamada; Masao Tomonaga; Hiroyuki Moriuchi; Yoshiro Tsuji; Shimeru Kamihira

2000-01-01

220

Antitumor Effects of Human Recombinant Interleukin6 on Acute Myeloid Leukemia in Mice and in Cell Cultures  

Microsoft Academic Search

Interleukin-6 (IL-6) has been shown to inhibit growth and induce differentiation of several myeloid leukemia cell lines. In this work, two in vivo models of acute myeloid leukemia (AML) in mice have been used to test the therapeutic potential of recombinant human IL-6. In mice inoculated by a transplantable AML tumor, IL-6 injections inhibited the devel- opment of leukemia and

Tamar Givon; Shimon Slavin; Nechama Haran-Ghera; Rita Michalevicz; Michel Revel

1992-01-01

221

Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells.  

PubMed

Pterostilbene, a polyphenolic compound present in grapes and other fruits, has been demonstrated to inhibit growth and induce apoptosis and autophagy in some cancer cell types. We found that pterostilbene at the IC(90) concentration of 44 µM inhibited proliferation and induced apoptosis in MOLT4 human leukemia cells. Treatment with pterostilbene resulted in a transient accumulation of cells in the G(0)/G(1)-cell cycle phase followed by the S-phase arrest. Pterostilbene-induced apoptotic death of MOLT4 cells was mediated by caspase-3 activation and was accompanied by the disruption of mitochondrial membrane potential, phosphatidylserine externalization and internucleosomal DNA fragmentation. Our results suggest that pterostilbene could serve as a potential additional chemotherapeutic agent for the treatment of leukemia. PMID:23264221

Siedlecka-Kroplewska, Kamila; Jozwik, Agnieszka; Kaszubowska, Lucyna; Kowalczyk, Anna; Boguslawski, Wojciech

2012-01-01

222

Characterization of lymphoid cells by two-dimensional mini gel electrophoresis of proteins  

Microsoft Academic Search

Cytosol proteins from normal lymphocytes, leukemic lymphocytes, and different cultured lymphoid cell lines were separated by two-dimensional mini gel electrophoresis. By staining with Coomassie blue, specific protein patterns were obtained. Very similar gel maps were producted by the cytosol proteins of chronic lymphocytic leukemia cells, hairy cells, and of in vitro grown B cells. Protein 36\\/6.2 (molecular weight\\/isoelectric point), consistently

F. W. Hirsch; C. Bröckl; K. J. Bross; G. Dölken

1983-01-01

223

Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens  

Microsoft Academic Search

Recently, the focus is on new specific immunotherapies for AML such as cellular therapies employing dendritic cells (DCs) generated from AML blasts. AML-DCs express constitutionally leukemia-associated antigens (LAAs) present in AML blasts they are generated from. Here we investigated whether the generation of AML-DCs would alter the expression level of LAAs. Moreover, we evaluated the presence of HLA and costimulatory

Li Li; Peter Reinhardt; Anita Schmitt; Thomas F. E. Barth; Jochen Greiner; Mark Ringhoffer; Hartmut Döhner; Markus Wiesneth; Michael Schmitt

2005-01-01

224

Apoptosis\\/differentiation-inducing effects of vitamin K2 on HL60 cells: dichotomous nature of vitamin K2 in leukemia cells  

Microsoft Academic Search

We originally reported that vitamin K2 (VK2) analogs, including menaquinone 4 (MK4) but not vitamin K1, effectively induce apoptosis in various types of primary cultured leukemia cells and leukemia cell lines in vitro. It has also been reported by others that VK2 showed the differentiation-inducing activity in leukemia cell lines. To investigate the discrepancy between apoptosis- and differentiation-inductions of leukemia

K Miyazawa; M Yaguchi; K Funato; A Gotoh; Y Kawanishi; Y Nishizawa; A Yuo; K Ohyashiki

2001-01-01

225

Membrane transport of mitoxantrone by L1210 leukemia cells.  

PubMed

Transport of radiolabeled mitoxantrone, a new antineoplastic agent, was studied using cultured mouse L1210 leukemia cells. The initial velocity of influx remained linear for about 90 sec and was 110 pmoles/10(6) cells measured at 60 sec. The steady-state accumulation of about 480 pmoles/10(6) cells was not reached until 30 min. The unidirectional drug influx was linear from 0 to 1000 microM extracellular drug concentration. The initial uptake was relatively temperature independent between 37 degrees and 27 degrees, but accumulation at steady state was 17% lower at 27 degrees. None of six metabolic inhibitors had an appreciable effect on initial uptake. Efflux was initially exponential with a half-life of 2.8 min; this efflux and the residual drug concentration plateau were not affected by KCN or verapamil. Under steady-state conditions, about 86% of the cell-associated label was contained in parent drug and the remainder in an unidentified metabolite. These studies indicate that the mechanism of mitoxantrone uptake is passive diffusion. The efflux is not energy requiring, but there is considerable tight binding of the drug to cellular structures. PMID:3566786

Burns, C P; Haugstad, B N; North, J A

1987-03-15

226

Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses.  

PubMed Central

Human T-cell leukemia virus (HTLV) is the etiologic agent of adult T-cell leukemia (ATL), a malignancy of T lymphocytes that is characterized by a long latency period after virus exposure. Intraperitoneal inoculation of severe combined immunodeficient (SCID) mice with HTLV-transformed cell lines and ATL tumor cells was employed to investigate the tumorigenic potential of HTLV type I (HTLV-I)-infected cells. In contrast to inoculation of ATL (RV-ATL) cells into SCID mice, which resulted in the formation of lymphomas, inoculation of HTLV-I- and HTLV-II-transformed cell lines (SLB-I and JLB-II cells, respectively) did not result in tumor formation. Immunosuppression of SCID mice, either by whole-body irradiation or by treatment with an antiserum, anti-asialo GM1 (alpha-AGM1), which transiently abrogates natural killer cell activity in vivo, was necessary to establish the growth of tumors derived from HTLV-transformed cell lines. PCR and flow cytometric studies reveal that HTLV-I-transformed cells are eliminated from the peritoneal cavities of inoculated mice by 3 days postinoculation; in contrast, RV-ATL cells persist and are detected until the mice succumb to lymphoma development. The differing behaviors of HTLV-infected cell lines and ATL tumor cells in SCID mice suggest that ATL cells have a higher tumorigenic potential in vivo than do HTLV-infected cell lines because of their ability to evade natural killer cell-mediated cytolysis.

Feuer, G; Stewart, S A; Baird, S M; Lee, F; Feuer, R; Chen, I S

1995-01-01

227

Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction.  

PubMed

The traditional view is that cancer cells predominately produce ATP by glycolysis, rather than by oxidation of energy-providing substrates. Mitochondrial uncoupling--the continuing reduction of oxygen without ATP synthesis--has recently been shown in leukemia cells to circumvent the ability of oxygen to inhibit glycolysis, and may promote the metabolic preference for glycolysis by shifting from pyruvate oxidation to fatty acid oxidation (FAO). Here we have demonstrated that pharmacologic inhibition of FAO with etomoxir or ranolazine inhibited proliferation and sensitized human leukemia cells--cultured alone or on bone marrow stromal cells--to apoptosis induction by ABT-737, a molecule that releases proapoptotic Bcl-2 proteins such as Bak from antiapoptotic family members. Likewise, treatment with the fatty acid synthase/lipolysis inhibitor orlistat also sensitized leukemia cells to ABT-737, which supports the notion that fatty acids promote cell survival. Mechanistically, we generated evidence suggesting that FAO regulates the activity of Bak-dependent mitochondrial permeability transition. Importantly, etomoxir decreased the number of quiescent leukemia progenitor cells in approximately 50% of primary human acute myeloid leukemia samples and, when combined with either ABT-737 or cytosine arabinoside, provided substantial therapeutic benefit in a murine model of leukemia. The results support the concept of FAO inhibitors as a therapeutic strategy in hematological malignancies. PMID:20038799

Samudio, Ismael; Harmancey, Romain; Fiegl, Michael; Kantarjian, Hagop; Konopleva, Marina; Korchin, Borys; Kaluarachchi, Kumar; Bornmann, William; Duvvuri, Seshagiri; Taegtmeyer, Heinrich; Andreeff, Michael

2009-12-21

228

Enhanced leukemia cell detection using a novel magnetic needle and nanoparticles  

PubMed Central

Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. While bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that employs antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) and directed against the acute leukemia antigen CD34, coupled with a “magnetic needle” biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34-conjugated SPIONs. Three separate approaches including microscopy, Superconducting Quantum Interference Device (SQUID) magnetometry, and in vitro magnetic needle extraction were then employed to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by ten-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared to the current standard of care.

Jaetao, Jason E.; Butler, Kimberly S.; Adolphi, Natalie L.; Lovato, Debbie M.; Bryant, Howard C.; Rabinowitz, Ian; Winter, Stuart S.; Tessier, Trace E.; Hathaway, Helen J.; Bergemann, Christian; Flynn, Edward R.; Larson, Richard S.

2009-01-01

229

Requirement of reactive oxygen species generation in apoptosis of leukemia cells induced by 2-methoxyestradiol  

Microsoft Academic Search

Aim:To investigate the effects of 2-methoxyestradiol (2-ME) on 2 myeloid leukemia cell lines HL-60 and U937, and to explore its mechanisms.Methods:Human myeloid leukemia cells HL-60 and U937 were used. Measurement of mitochondrial membrane potential (Dym) was performed using 5,5?,6,6?-Tetrachloro-1,1?,3,3?-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). Apoptosis and cellular nitricoxide (NO) were detected by flow cytometry using Annexin V and NO sensor dye. Superoxide anion

Miao-rong She; Jing-gao Li; Kun-yuan Guo; Wei Lin; Xin Du; Xin-qing Niu

2007-01-01

230

Immunophenotyping of surface antigens in acute myeloid leukemia by flow cytometry after red blood cell lysis  

Microsoft Academic Search

Immunophenotyping of acute leukemia using flow cytometry after density gradient separation (dg-sep) of mononuclear cells is the international gold standard. But destroying red cells by whole blood lysis (wb-lysis) after direct staining has found a broad usage.Both methods revealed congruent results in phenotyping of 26 cases of acute myeloid leukemias by testing CD4, CD7, CD11b, CD11c, CD13, CD14, CD15, CD33,

Martin Schwonzen; Volker Diehl; Mario Dellanna; Peter Staib

2007-01-01

231

Fusion of bovine leukemia virus with target cells monitored by R18 fluorescence and PCR assays.  

PubMed

PCR and R18 fluorescence dequenching assays have been combined to monitor the kinetics of fusion of bovine leukemia virus with target cells (CC81, OVK, or Raji). Antibodies raised against gp51 allow us to demonstrate that not only the hydrophobic N-terminal domain of the transmembrane glycoprotein gp30 but also specific domains of gp51 (amino acids 39 to 103) are involved in bovine leukemia virus-cell fusion. PMID:8985408

Zarkik, S; Defrise-Quertain, F; Portetelle, D; Burny, A; Ruysschaert, J M

1997-01-01

232

Fusion of bovine leukemia virus with target cells monitored by R18 fluorescence and PCR assays.  

PubMed Central

PCR and R18 fluorescence dequenching assays have been combined to monitor the kinetics of fusion of bovine leukemia virus with target cells (CC81, OVK, or Raji). Antibodies raised against gp51 allow us to demonstrate that not only the hydrophobic N-terminal domain of the transmembrane glycoprotein gp30 but also specific domains of gp51 (amino acids 39 to 103) are involved in bovine leukemia virus-cell fusion.

Zarkik, S; Defrise-Quertain, F; Portetelle, D; Burny, A; Ruysschaert, J M

1997-01-01

233

Isolation and Characterization of Simian T-Cell Leukemia Virus Type II from New World Monkeys  

Microsoft Academic Search

Since the description of human T-cell leukemia virus type I (HTLV-I) and its simian counterpart, simian T-cell leukemia virus type I (STLV-I), the possible existence of other related simian retroviruses has been raised. Here, we report a new retrovirus, STLV-II, which we have identifled in spider monkeys (Áteles fusciceps), a New World primate species. Initially, a recombinant HTLV-II envelope protein

YI-MING A. CHEN; YNG-JU JANG; RICHARD J. MONTALI; PHYLLIS J. KANKI; QIAN-CHUN YU; JAANG-JIUN WANG; KENNETH P. SAMUEL; TAKIS S. PAPAS

234

Malignant lymphomas in Japan: Epidemiological analysis of adult T-cell leukemia\\/lymphoma (ATL)  

Microsoft Academic Search

The incidence of malignant lymphomas in Japan is relatively low compared to that in western European countries and the United States. However, in limited areas in Japan a specific type of lymphoid malignancy called adult T-cell leukemia\\/lymphoma (ATL), which is caused by human T-cell leukemia virus type I (HTLV-I), is highly prevalent, and there are also many healthy carriers of

Kazuo Tajima

1988-01-01

235

Current Status of Therapeutic Approaches to Adult T-Cell Leukemia  

Microsoft Academic Search

More than 2 decades have elapsed since the proposal of adult T-cell leukemia (ATL). Since then, the discovery of the etiologic\\u000a virus, human T-cell leukemia virus type I (HTLV-I), and the establishment of the diagnostic steps of serum test and molecular\\u000a study have clearly defined ATL as a distinct disease entity. Because conventional chemotherapy, which is active against other\\u000a lymphoid

Takayuki Ishikawa

2003-01-01

236

Critical molecular pathways in cancer stem cells of chronic myeloid leukemia  

Microsoft Academic Search

Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations

Y Chen; C Peng; C Sullivan; D Li; S Li

2010-01-01

237

Targeting the B cell receptor pathway in chronic lymphocytic leukemia.  

PubMed

The B cell receptor (BCR) pathway plays a crucial role in the survival, proliferation and trafficking of chronic lymphocytic leukemia (CLL) cells. Inhibitors of the key kinases in this pathway, including spleen tyrosine kinase (SYK), mammalian target of rapamycin (mTOR), phosphoinositide 3'-kinase (PI3K) and Bruton's tyrosine kinase (BTK), have been found in preclinical models to decrease CLL cell viability both directly and indirectly through modulation of the microenvironment. Recently, oral agents targeting each of these kinases have been explored in early phase clinical trials in patients with CLL. BCR pathway antagonists appear to be highly active in relapsed/refractory CLL, independent of high-risk disease markers such as del(17p). These agents have shown a unique pattern of inducing early transient lymphocytosis, which typically is associated with nodal response. Here, we review the biology of the BCR, the kinases within this pathway and their interaction with the CLL microenvironment. We also discuss data from recent and ongoing clinical trials of BCR antagonists. We address the development of potential biomarkers for response to these agents such as ZAP-70, IGHV status and CCL3, and discuss where these exciting new drugs may fit in the evolving landscape of CLL therapy. PMID:22616724

Davids, Matthew S; Brown, Jennifer R

2012-12-01

238

IgE synthesis by chronic lymphocytic leukemia cells  

PubMed Central

The present results indicate that B cells isolated from chronic lymphocytic leukemia (B-CLL) from 11 of 14 patients are capable of specifically producing IgE upon costimulation with IL-4 and hydrocortisone (HC). IgE is detected by intracytoplasmic fluorescence staining and by RIA. Clinical, hematological, and immunological parameters (including Rai stage, WBC, Lc, sIg kappa/lambda, CD5, and CD23 expression) cannot distinguish the IgE responder from the nonresponder patients. IL-4 alone is a potent inducer of human IgE synthesis by normal PBMC and we show here that its effect is strikingly enhanced by HC. The IgE produced by B-CLLs are monoclonal since they display the same L chain type as the freshly isolated CD5+ B-CLLs. We, therefore, conclude that the combination of IL-4 and HC can abrogate the maturation arrest of CD5+ B-CLLs by inducing their differentiation into IgE-producing cells. The present data provide a unique model to study the isotype switching to IgE and the regulation of human IgE synthesis by monoclonal human B cells.

1989-01-01

239

Identification of the Gross cell surface antigen associated with murine leukemia virus-infected cells.  

PubMed Central

The Gross cell surface antigen (GCSA) is produced by cells that are either exogenously infected with murine leukemia virus (MuLV) or are expressing endogenous MuLV genomes. In immune precipitation assays, GCSA was resolved into two serologically distinct 85,000- and 95,000-dalton viral proteins. These antigenic components are glycosylated forms of the polyprotein precursors of the MuLV internal structural proteins. Images

Ledbetter, J; Nowinski, R C

1977-01-01

240

Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL)  

PubMed Central

The clinical entity of adult T-cell leukemia (ATL) was established around 1977, and human T-cell leukemia virus type 1 (HTLV-I) was subsequently identified in 1980. In the 25 years since the discovery of HTLV-I, HTLV-I infection and its associated diseases have been extensively studied, and many of their aspects have been clarified. However, the detailed mechanism of leukemogenesis remains unsolved yet, and the prognosis of ATL patients still poor because of its resistance to chemotherapy and immunodeficiency. In this review, I highlight the recent progress and remaining enigmas in HTLV-I infection and its associated diseases, especially ATL.

Matsuoka, Masao

2005-01-01

241

GATA-2 mediated regulation of normal hematopoietic stem/progenitor cell function, myelodysplasia and myeloid leukemia  

PubMed Central

Unremitting blood cell production throughout the lifetime of an organism is reliant on hematopoietic stem cells (HSCs). A rare and relatively quiescent cell type harbored in adult bone marrow, HSCs are, on entry into cell cycle fated to self-renew, undergo apoptosis or differentiate to progenitors (HPCs) that eventually yield specific classes of blood cells. Disruption of these HSC cell fate decisions is considered to be fundamental to the development of leukemia. Much effort has therefore been placed on understanding the molecular pathways that regulate HSC cell fate decisions and how these processes are undermined during leukemia. Transcription factors have emerged as critical regulators in this respect. Here we review the participation of zinc finger transcription factor GATA-2 in regulating normal hematopoietic stem and progenitor cell functionality, myelodysplasia and myeloid leukemia.

Rodrigues, Neil P.; Tipping, Alex J.; Wang, Zhengke; Enver, Tariq

2011-01-01

242

Emodin Induces Apoptotic Death in Murine Myelomonocytic Leukemia WEHI-3 Cells In Vitro and Enhances Phagocytosis in Leukemia Mice In Vivo  

PubMed Central

Emodin is one of major compounds in rhubarb (Rheum palmatum L.), a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3) and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24?h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca2+ and reduced the level of ??m by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.

Chang, Yuan-Chang; Lai, Tung-Yuan; Yu, Chun-Shu; Chen, Hung-Yi; Yang, Jai-Sing; Chueh, Fu-Shin; Lu, Chi-Cheng; Chiang, Jo-Hua; Huang, Wen-Wen; Ma, Chia-Yu; Chung, Jing-Gung

2011-01-01

243

Graft-versus-Tax Response in Adult T-Cell Leukemia Patients after Hematopoietic Stem Cell Transplantation  

Microsoft Academic Search

Adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) is characterized by poor prognosis after chemotherapy. Recent clinical trials have indicated, however, that allogeneic but not autologous hematopoietic stem cell transplantation (HSCT) for ATL can yield better clinical outcomes. In the present study, we investigated cellu- lar immune responses of ATL patients who obtained complete remission

Nanae Harashima; Kiyoshi Kurihara; Atae Utsunomiya; Ryuji Tanosaki; Shino Hanabuchi; Masato Masuda; Takashi Ohashi; Fumiyo Fukui; Atsuhiko Hasegawa; Takao Masuda; Yoichi Takaue; Jun Okamura; Mari Kannagi

2004-01-01

244

Differentiation and Retrodifferentiation of Human Myeloid Leukemia Cells Is Associated with Reversible Induction of Cell Cycle-regulatory Genes1  

Microsoft Academic Search

Treatment of human myeloid leukemia cells (HL-60, U-937, THP-I) with the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) is associated with differentiation along the monocytic lineage. This induc tion by TPA is characterized in part by growth arrest and the appearance of differentiated monocytic phenotype. The present studies demonstrate that myeloid leukemia cells exit the cell cycle to G0-G, between 24 and 36

Ralf I; Hisato Gunji; Rakesh Datta; Surender Kharbanda; Andreas Hartmann; Ralph Weichselbaum; Donald Kufe

1992-01-01

245

Nanoarchitectured electrochemical cytosensors for selective detection of leukemia cells and quantitative evaluation of death receptor expression on cell surfaces.  

PubMed

The variable susceptibility to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment observed in various types of leukemia cells is related to the difference in the expression levels of death receptors, DR4 and DR5, on the cell surfaces. Quantifying the DR4/DR5 expression status on leukemia cell surfaces is of vital importance to the development of diagnostic tools to guide death receptor-based leukemia treatment. Taking the full advantages of novel nanobiotechnology, we have developed a robust electrochemical cytosensing approach toward ultrasensitive detection of leukemia cells with detection limit as low as ~40 cells and quantitative evaluation of DR4/DR5 expression on leukemia cell surfaces. The optimization of electron transfer and cell capture processes at specifically tailored nanobiointerfaces and the incorporation of multiple functions into rationally designed nanoprobes provide unique opportunities of integrating high specificity and signal amplification on one electrochemical cytosensor. The high sensitivity and selectivity of this electrochemical cytosensing approach also allows us to evaluate the dynamic alteration of DR4/DR5 expression on the surfaces of living cells in response to drug treatments. Using the TRAIL-resistant HL-60 cells and TRAIL-sensitive Jurkat cells as model cells, we have further verified that the TRAIL susceptibility of various types of leukemia cells is directly correlated to the surface expression levels of DR4/DR5. This versatile electrochemical cytosensing platform is believed to be of great clinical value for the early diagnosis of human leukemia and the evaluation of therapeutic effects on leukemia patients after radiation therapy or drug treatment. PMID:23621478

Zheng, Tingting; Fu, Jia-Ju; Hu, Lihui; Qiu, Fan; Hu, Minjin; Zhu, Jun-Jie; Hua, Zi-Chun; Wang, Hui

2013-05-14

246

NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches  

Microsoft Academic Search

BackgroundLeukemia initiating cells (LIC) contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL) and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in

Wenxue Ma; Alejandro Gutierrez; Daniel J. Goff; Ifat Geron; Anil Sadarangani; Christina A. M. Jamieson; Angela C. Court; Alice Y. Shih; Qingfei Jiang; Christina C. Wu; Kang Li; Kristen M. Smith; Leslie A. Crews; Neil W. Gibson; Ida Deichaite; Sheldon R. Morris; Ping Wei; Dennis A. Carson; A. Thomas Look; Catriona H. M. Jamieson

2012-01-01

247

Clonal selection in xenografted human T cell acute lymphoblastic leukemia recapitulates gain of malignancy at relapse  

PubMed Central

Genomic studies in human acute lymphoblastic leukemia (ALL) have revealed clonal heterogeneity at diagnosis and clonal evolution at relapse. In this study, we used genome-wide profiling to compare human T cell ALL samples at the time of diagnosis and after engraftment (xenograft) into immunodeficient recipient mice. Compared with paired diagnosis samples, the xenograft leukemia often contained additional genomic lesions in established human oncogenes and/or tumor suppressor genes. Mimicking such genomic lesions by short hairpin RNA–mediated knockdown in diagnosis samples conferred a selective advantage in competitive engraftment experiments, demonstrating that additional lesions can be drivers of increased leukemia-initiating activity. In addition, the xenograft leukemias appeared to arise from minor subclones existing in the patient at diagnosis. Comparison of paired diagnosis and relapse samples showed that, with regard to genetic lesions, xenograft leukemias more frequently more closely resembled relapse samples than bulk diagnosis samples. Moreover, a cell cycle– and mitosis-associated gene expression signature was present in xenograft and relapse samples, and xenograft leukemia exhibited diminished sensitivity to drugs. Thus, the establishment of human leukemia in immunodeficient mice selects and expands a more aggressive malignancy, recapitulating the process of relapse in patients. These findings may contribute to the design of novel strategies to prevent or treat relapse.

Clappier, Emmanuelle; Gerby, Bastien; Sigaux, Francois; Delord, Marc; Touzri, Farah; Hernandez, Lucie; Ballerini, Paola; Baruchel, Andre

2011-01-01

248

[Dendritic cell-based therapeutic vaccination for acute myeloid leukemia].  

PubMed

The long-term outlook for adult patients with acute myeloid leukemia (AML) remains dismal. The main reason for this state of affairs lies in the fact that the majority of AML patients will eventually relapse, even after obtaining complete remission following front-line chemotherapy. Relapses are generally attributed to the persistence of a small number of chemotherapy-resistant leukemic (stem) cells, a condition known as minimal residual disease (MRD). The eradication of MRD, with the eventual aim of reducing the risk of relapse, therefore represents a high-priority goal of modern AML therapy. It is now well established that the immune system plays a crucial role in the defense against AML. This knowledge has fuelled the development of immune-based approaches to control MRD and, ultimately, to prevent relapse. One of the promising strategies that have emerged in this regard involves the use of dendritic cells for therapeutic vaccination. This review article aims to introduce the reader into the conceptual and practical aspects of DC-based vaccination for AML. Next, we will review the first clinical results obtained with this immunotherapeutic approach in AML patients. Finally, we will briefly reflect on the potential place of DC vaccination in the future therapy of AML. PMID:22641288

Anguille, Sébastien; Van Tendeloo, Vigor; Berneman, Zwi

2012-06-01

249

Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells.  

PubMed

Ezrin links the actin filaments with the cell membrane and has a functional role in the apoptotic process. It appears clear that ezrin is directly associated with Fas, leading to activation of caspase cascade and cell death. However, the exact role of ezrin in ursolic acid (UA)-induced apoptosis remains unclear. In this study, we show for the first time that UA induces apoptosis in both transformed and primary leukemia cells through dephosphorylation/downregulation of ezrin, association and polarized colocalization of Fas and ezrin, as well as formation of death-inducing signaling complex. These events are dependent on Rho-ROCK1 signaling pathway. Knockdown of ezrin enhanced cell death mediated by UA, whereas overexpression of ezrin attenuated UA-induced apoptosis. Our in vivo study also showed that UA-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with the dephosphorylation/downregulation of ezrin. Such findings suggest that the cytoskeletal protein ezrin may represent an attractive target for UA-mediated lethality in human leukemia cells. PMID:23584398

Li, G; Zhou, T; Liu, L; Chen, J; Zhao, Z; Peng, Y; Li, P; Gao, N

2013-04-12

250

Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells  

PubMed Central

Ezrin links the actin filaments with the cell membrane and has a functional role in the apoptotic process. It appears clear that ezrin is directly associated with Fas, leading to activation of caspase cascade and cell death. However, the exact role of ezrin in ursolic acid (UA)-induced apoptosis remains unclear. In this study, we show for the first time that UA induces apoptosis in both transformed and primary leukemia cells through dephosphorylation/downregulation of ezrin, association and polarized colocalization of Fas and ezrin, as well as formation of death-inducing signaling complex. These events are dependent on Rho-ROCK1 signaling pathway. Knockdown of ezrin enhanced cell death mediated by UA, whereas overexpression of ezrin attenuated UA-induced apoptosis. Our in vivo study also showed that UA-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with the dephosphorylation/downregulation of ezrin. Such findings suggest that the cytoskeletal protein ezrin may represent an attractive target for UA-mediated lethality in human leukemia cells.

Li, G; Zhou, T; Liu, L; Chen, J; Zhao, Z; Peng, Y; Li, P; Gao, N

2013-01-01

251

Change in surface properties of rat basophilic leukemia cells caused by adhesion to solid substrate  

Microsoft Academic Search

Rat basophilic leukemia cells (RBL) change their functional properties when they adhere to a solid substrate. The change in the functional property of RBL cells may be accompanied by some change in electrokinetic properties of the cell surfaces. The adhesion to a glass surface can be suppressed temporarily by suspending the cells in a teflon tube. In the present paper

Kimiko Makino; Fumio Fukai; Tatsuya Kawaguchi; Hiroyuki Ohshima

1995-01-01

252

Selection of a WEHI-3B leukemia cell subclone resistant to inhibition by cholera toxin  

Microsoft Academic Search

The studies on the inhibitory effect exerted by Cholera Toxin (CT) on cell growth and proliferation indicate a remarkable heterogeneity of cell response suggesting that the inhibition represents the final event of many different ways or mechanisms . After CT binding, cAMP accumulation may not occur (as in L1210 leukemia cells) or, when occurring (as in SR-4987 stromal cells), may

Augusto Pessina; Attilia Giuliani; Cristina Croera; Paola Foti; Lucia Mascolo; Giuseppina Gagliardi; Maria Grazia Neri

2002-01-01

253

[Synthesis of emodin derivatives and their inhibiting effects on proliferation of leukemia cell lines].  

PubMed

The aim of this study was to explore the inhibitory effect of newly synthesised emodin derivatives on the proliferation of leukemia cell lines and to select the most effective one from these emodin derivatives for further research. Emodin derivatives were synthesized by modifying the structure of emodin. MTT method was used to detect the proliferative inhibition in leukemia cell lines treated with emodin derivatives. The results showed that the half inhibitory concentration (IC50) for K562 cells treated with emodin derivatives E10-19 for 48 h was 0.84 - 12.01 µmol/L. E19 displayed the best anti-proliferative activity, while E16 and E17 did not show effects on K562 cells. Emodin derivative E19 was chosen for treating U937, NB4, Molt-4 and CA-46 cells, their IC50 for 48 h were 0.85, 0.9, 0.76, 0.8 µmol/L respectively. The IC50 of E19 for LQ2 cells was 3.60 µmol/L, and the IC50 range of E19 for normal human peripheral blood mononuclear cells at 48 h was 4.01 - 4.78 µmol/L. It is concluded that emodin derivative E19 can strongly inhibit the growth of leukemia cells and its inhibiting effect on proliferation of leukemia cells has a certain specificity. The specific mechanism of E19 anti-leukemia effect should be further studied. PMID:23484691

Zheng, Jun-Ting; Wang, Wen-Feng; Li, Jing; Zheng, Zhi-Hong; Liu, Ting-Bo; Hu, Jian-Da

2013-02-01

254

Anti-JL1 antibody-conjugated poly ( l-lysine) for targeted gene delivery to leukemia T cells  

Microsoft Academic Search

We have designed the gene delivery carrier targeted to Molt 4 cells, human leukemia T cells, using monoclonal antibody against leukemia-specific JL1 antigen, anti-JL1 antibody, as a targeting moiety. Anti-JL1 antibody has been proven to bind to JL1 antigen and subsequently be internalized into Molt 4 cells, demonstrating that anti-JL1 antibody has the potential as a targeting ligand for leukemia-specific

Wonhee Suh; June-Key Chung; Seong-Hoe Park; Sung Wan Kim

2001-01-01

255

Yarn hairiness parameterization using a coherent signal processing technique  

Microsoft Academic Search

The aim of this paper is to present an automatic yarn hairiness parameterization method based on optical sensors. Hairiness measurements are performed using a coherent signal processing technique for higher resolution. Using this optical technique together with electronic instrumentation and custom developed software, it is possible to quantify all traditional hairiness parameters (i.e. hairiness (H), its coefficient of variation (CVH)

Vítor Carvalho; Paulo Cardoso; Michael Belsley; Rosa M. Vasconcelos; Filomena O. Soares

2008-01-01

256

Characteristics of. beta. -adrenoreceptors of cells of leukemia L1210 and its sarcolysin-resistant variant  

SciTech Connect

The authors attempt to discover possible correlations between the sensitivity of tumor cells to sarcolysin and the characteristic features of the beta-adrenoreceptors of these cells. They study the effect of beta-adrenoreceptors and their characteristics in cells of leukemia L1210 sensitive and resistant to sarcolysin. Mouse leukemia cells were used in the experiments and the tumor cell suspension was incubated with increasing concentrations of the beta-adrenoblocker L-/sup 3/H-dihydroalprenolol in the presence or absence of L-propranolol.

Khabarov, S.V.

1987-11-01

257

Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation  

PubMed Central

Eltrombopag (EP) is a small-molecule, nonpeptide thrombopoietin receptor (TPO-R) agonist that has been approved recently for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpura. Prior studies have shown that EP stimulates megakaryopoiesis in BM cells from patients with acute myeloid leukemia and myelodysplastic syndrome, and the results also suggested that it may inhibit leukemia cell growth. In the present study, we studied the effects of EP on leukemia cell proliferation and the mechanism of its antiproliferative effects. We found that EP leads to a decreased cell division rate, a block in G1 phase of cell cycle, and increased differentiation in human and murine leukemia cells. Because EP is species specific in that it can only bind TPO-R in human and primate cells, these findings further suggested that the antileukemic effect is independent of TPO-R. We found that treatment with EP leads to a reduction in free intracellular iron in leukemic cells in a dose-dependent manner. Experimental increase of intracellular iron abrogated the antiproliferative and differentiation-inducing effects of EP, demonstrating that its antileukemic effects are mediated through modulation of intracellular iron content. Finally, determination of EP's antileukemic activity in vivo demonstrated its ability to prolong survival in 2 mouse models of leukemia.

Roth, Michael; Will, Britta; Simkin, Guillermo; Narayanagari, Swathi; Barreyro, Laura; Bartholdy, Boris; Tamari, Roni; Mitsiades, Constantine S.; Verma, Amit

2012-01-01

258

Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association.  

PubMed

Cold agglutinin induced autoimmune hemolytic anemia is uncommonly associated with leukemia and lymphomas. We present a case of a young Mexican female presenting with a cold agglutinin hemolytic anemia with expression of a rare Pr antigen specificity and an aggressive NK-cell leukemia. Our patient had a rapid fatal course. To our knowledge this is the first reported case of such an association. PMID:17301976

Skorupa, Amy; Chaudhary, Uzair B; Lazarchick, John

2007-07-01

259

Gene Rearrangements in Bone Marrow Cells of Patients with Acute Myelogenous Leukemia  

Microsoft Academic Search

At diagnosis, clonal gene rearrangement probes [retinoic acid receptor (RAR)-?, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-?, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients

H. M. Schmetzer; S. Braun; D. Wiesner; T. Duell; H. H. Gerhartz; J. Mittermueller

2000-01-01

260

Lapatinib Induces Autophagy, Apoptosis and Megakaryocytic Differentiation in Chronic Myelogenous Leukemia K562 Cells  

Microsoft Academic Search

Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB\\/Her) in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML) K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied

Huey-Lan Huang; Yu-Chieh Chen; Yu-Chuen Huang; Kai-Chien Yang; Hsin yi Pan; Shou-Ping Shih; Yu-Jen Chen

2011-01-01

261

Childhood Leukemia  

MedlinePLUS

... cells. It is the most common type of childhood cancer. Your blood cells form in your bone ... in the bones or joints Risk factors for childhood leukemia include having a brother or sister with ...

262

Cell Surface Antigens Associated with Murine Leukemia Virus: Definition of the GL and GT Antigenic Systems  

PubMed Central

Two new serological specificities were identified on the surface of murine leukemia virus (MuLV)-infected cells by direct and absorption immunofluorescence tests. Both antigens were detected with antisera prepared in rats that were growing transplants of syngenic MuLV-induced leukemias. Antigen GL was defined with the AKR leukemia K36 as the test cell; antigen GT was defined with the W/Fu leukemia C58(NT)D as the test cell. GL and GT antigens were serologically and genetically independent of the MuLV-induced Gross and GIX cell-surface antigens. GL and GT antigens were found in normal lymphoid cells of mice from high-leukemic strains, but not in lymphoid tissues of mice from most low-leukemic strains. Tumors and leukemias of mice of low-leukemic strains often were GL and GT positive. Similarly, infection of normal cells with MuLV resulted in expression of GL and GT. With ferritin-labeled antibody the GL and GT antigens were observed on virus-free segments of the cell surface. Genetically, GL and GT antigens were each controlled by two dominant unlinked genes in AKR mice; these same antigens were each controlled by three or more dominant unlinked genes in C58 mice. Penetrance of GL and GT regulatory genes was dependent upon the Fv-1 genotype of the host. Expression of GL antigen was closely associated with virus production, whereas expression of GT antigen was less closely associated.

Nowinski, Robert C.; Peters, Elizabeth D.

1973-01-01

263

Hyoscyamine biosynthesis in Datura stramonium hairy root in vitro systems with different ploidy levels.  

PubMed

Hyoscyamine biosynthesis in Datura stramonium hairy roots with different ploidy levels was investigated. For the first time, we report that hairy roots undergo endoreduplication and therefore consist mainly of cells with doupled sets of chromosomes of primary plant tissues, used for Agrobacterium transformation. The alkaloid profiles of hairy roots obtained from diploid and tetraploid plants were similar in terms of the major compounds, but they differed significantly with respect to the minor compounds (here defined as those that accounted for <1% of the total ion current of the alkaloid mixture in gas chromatography-mass spectrometric analyses). Significant differences in the effects of the main nutrients on the growth of the hairy roots obtained from diploid and tetraploid plants and their hyoscyamine contents were observed. The maximal yield of hyoscyamine (177 mg/L) was obtained when hairy roots from tetraploid plants were cultivated in Murashige-Skoog nutrient medium supplemented with 6% sucrose. Time courses of utilization of the main nutrients in the medium during cultivation of D. stramonium hairy root cultures are also presented. PMID:18509605

Pavlov, A; Berkov, S; Weber, J; Bley, Th

2008-05-29

264

NKT cell-dependent leukemia eradication following stem cell mobilization with potent G-CSF analogs  

PubMed Central

NKT cells have pivotal roles in immune regulation and tumor immunosurveillance. We report that the G-CSF and FMS-like tyrosine kinase 3 ligand (Flt-3L) chimeric cytokine, progenipoietin-1, markedly expands the splenic and hepatic NKT cell population and enhances functional responses to ?-galactosylceramide. In a murine model of allogeneic stem cell transplantation, donor NKT cells promoted host DC activation and enhanced perforin-restricted CD8+ T cell cytotoxicity against host-type antigens. Following leukemic challenge, donor treatment with progenipoietin-1 significantly improved overall survival when compared with G-CSF or control, attributable to reduced graft-versus-host disease mortality and paradoxical augmentation of graft-versus-leukemia (GVL) effects. Enhanced cellular cytotoxicity was dependent on donor NKT cells, and leukemia clearance was profoundly impaired in recipients of NKT cell–deficient grafts. Enhanced cytotoxicity and GVL effects were not associated with Flt-3L signaling or effects on DCs but were reproduced by prolonged G-CSF receptor engagement with pegylated G-CSF. Thus, modified G-CSF signaling during stem cell mobilization augments NKT cell–dependent CD8+ cytotoxicity, effectively separating graft-versus-host disease and GVL and greatly expanding the potential applicability of allogeneic stem cell transplantation for the therapy of malignant disease.

Morris, Edward S.; MacDonald, Kelli P.A.; Rowe, Vanessa; Banovic, Tatjana; Kuns, Rachel D.; Don, Alistair L.J.; Bofinger, Helen M.; Burman, Angela C.; Olver, Stuart D.; Kienzle, Norbert; Porcelli, Steven A.; Pellicci, Daniel G.; Godfrey, Dale I.; Smyth, Mark J.; Hill, Geoffrey R.

2005-01-01

265

Detection of Merkel cell polyomavirus in chronic lymphocytic leukemia T-cells.  

PubMed

Chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) is the most common B-cell leukemia/lymphoma, effecting >15,000 patients/year. There has been a proposed limited antigenic etiology, at least in some cases, of CLL/SLL based upon immunoglobulin heavy chain stereotypy found across unrelated cases, suggesting viral source may provide such antigenic stimulation. With an established epidemiological link between CLL/SLL and Merkel cell carcinoma (MCC), there has been some interest in investigating a possible leukemogenic role of Merkel cell polyomavirus (MCPyV), which is found in 80% of MCC cases. Recent studies have shown that MCPyV is present in lymphocytes in a small percentage of CLL/SLL cases, but the specific tropism for lymphocytes has not been well-established. In this study, we used quantitative PCR to investigate the presence of MCPyV in fluorescence activated cell sorted purified B- and T-cells from 23 CLL/SLL cases. Three of 23 cases (13%) had detectable MCPyV in T-cells, and none of the cases had detectable MCPyV in B-cells. These findings suggest that MCPyV may have tropism for T-cells in addition to previously reported neoplastic B-cells. PMID:23026399

Cimino, Patrick J; Bahler, David W; Duncavage, Eric J

2012-09-28

266

Kinetic Analysis of Human T-Cell Leukemia Virus Type 1 Gene Expression in Cell Culture and Infected Animals  

Microsoft Academic Search

Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell leukemia and is associated with a variety of lymphocyte-mediated disorders. It has been hypothesized that a highly regulated pattern of HTLV-1 gene expression is critical for virus survival and disease pathogenesis. In this study, real-time reverse transcriptase PCR was used to determine the kinetics of viral gene expression in

Min Li; Matthew Kesic; Han Yin; Lianbo Yu; Patrick L. Green

2009-01-01

267

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer  

ClinicalTrials.gov

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; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

2013-01-09

268

A possible association between HTLV-I and B-cell chronic lymphocytic leukemia in Jamaica.  

PubMed

Cell surface markers were determined in 10 patients with chronic lymphocytic leukemia (CLL) in Jamaica, an area endemic for the human T-cell leukemia/lymphoma virus (HTLV-I) and with a high positivity for HTLV-I antibody titers in CLL patients. The results demonstrated that the predominant cell phenotype in all patients was of B-cell origin. When surveyed for HTLV-I antibody, 3 out of 5 patients with B-CLL from this series were found positive. A possible association between HTLV-I and B-CLL is discussed. PMID:3000123

Hendriks, J

1985-01-01

269

Acute myeloid leukemia with T-cell receptor gamma gene rearrangement occurring in a patient with chronic lymphocytic leukemia: a case report.  

PubMed

The association of chronic lymphocytic leukemia (CLL) and acute leukemia, either lymphoid or myeloid is a rare event. Our review of the medical literature revealed only 6 cases of CLL transformation to acute myeloid leukemia (AML) (M0, M1 and M2) with no other associated malignancy. We report a similar case but with occurrence of AML-M4 associated with normal cytogenetic analysis and molecular testing but with positive T-cell receptor gamma gene rearrangement rather than the usual Vbeta rearrangement. PMID:16947317

Hatoum, Hassan A; Mahfouz, Rami A R; Otrock, Zaher K; Hudaib, Abdel-Rahman; Taher, Ali T; Shamseddine, Ali I

2007-01-01

270

A novel aptamer-based competition strategy for ultrasensitive electrochemical detection of leukemia cells.  

PubMed

A robust, nanobiotechnology-based electrochemical cytosensing platform for the detection of acute leukemia cells was developed with high sensitivity, selectivity, acceptable rapidity and excellent extensibility. It utilized the competitive binding of cell-specific aptamers to acute leukemia cells and subsequent voltammetric quantification of the metal signature. Greatly enhanced sensitivity was achieved with dual signal amplification by using Fe3O4 magnetic nanoparticles (MNPs) as carriers to load a large amount of gold nanoparticles (AuNPs) and AuNP-catalyzed silver deposition. The proposed competitive cytosensor showed high sensitivity with a detection limit down to 10 cells. This simple and low-cost electrochemical cytosensing approach offers great promise to extend its application to early detection of human leukemia and possibly to other cancer cells. PMID:23978949

Zhang, Kui; Tan, Tingting; Fu, Jia-Ju; Zheng, Tingting; Zhu, Jun-Jie

2013-09-30

271

Antiproliferative effects of 4?, 5?-unsaturated adenine nucleosides on leukemia L 1210 cells in vitro  

Microsoft Academic Search

Summary Several 4?, 5?-unsaturated adenine nucleosides were shown to have antiproliferative activity against L 1210 leukemia cells in vitro. The active nucleosides were cytotoxic to the L 1210 cells as demonstrated by Trypan Blue uptake. The cytotoxicity was not induced by alterations in the ribonucleoside and deoxyribonucleoside triphosphate levels of the L 1210 cells.

B. Sheid; L. M. Lerner; E. Gaetjens

1989-01-01

272

A role for GPx3 in activity of normal and leukemia stem cells.  

PubMed

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs. PMID:22508837

Herault, Olivier; Hope, Kristin J; Deneault, Eric; Mayotte, Nadine; Chagraoui, Jalila; Wilhelm, Brian T; Cellot, Sonia; Sauvageau, Martin; Andrade-Navarro, Miguel A; Hébert, Josée; Sauvageau, Guy

2012-04-16

273

A role for GPx3 in activity of normal and leukemia stem cells  

PubMed Central

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs.

Herault, Olivier; Hope, Kristin J.; Deneault, Eric; Mayotte, Nadine; Chagraoui, Jalila; Wilhelm, Brian T.; Cellot, Sonia; Sauvageau, Martin; Andrade-Navarro, Miguel A.; Hebert, Josee

2012-01-01

274

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?  

PubMed Central

Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.

Dorantes-Acosta, Elisa; Pelayo, Rosana

2012-01-01

275

Pomolic acid triggers mitochondria-dependent apoptotic cell death in leukemia cell line.  

PubMed

One of the major goals in chemotherapy is to circumvent anti-apoptotic strategies developed by tumor cells. In a previous paper, we showed that pomolic acid (PA) is able to kill the leukemia cell line K562 and its MDR derivative, Lucena 1. Here, we demonstrated that PA-induced apoptosis of HL-60 cells is dependent on the activation of caspases-3 and -9 and dissipation of the mitochondrial transmembrane potential (Deltapsim). Disruption of Deltapsim precedes caspase activation and is not inhibited by zVAD-fmk indicating mitochondria as the main target of PA. Our data pointed to the potential use of PA to overcome apoptosis resistance. PMID:15694664

Fernandes, Janaina; Weinlich, Ricardo; Castilho, Rachel Oliveira; Kaplan, Maria Auxiliadora Coelho; Amarante-Mendes, Gustavo Pessini; Gattass, Cerli Rocha

2005-02-28

276

Determinants of Sensitivity of Human T Cell Leukemia CCRF-CEM cells to Immucillin-H  

PubMed Central

Immucillin-H (BCX-1777, forodesine) is a transition state analogue and potent inhibitor of PNP that shows promise as a specific agent against activated human T-cells and T-cell leukemias. The immunosuppressive or antileukemic effects of Immucillin-H (ImmH) require co-administration with deoxyguanosine (dGuo) to attain therapeutic levels of intracellular dGTP. In this study we investigated the requirements for sensitivity and resistance to ImmH and dGuo. 3H-ImmH transport assays demonstrated that the equilibrative nucleoside transporters (ENT1 and ENT2) facilitated the uptake of ImmH in human leukemia CCRF-CEM cells whereas 3H-dGuo uptake was primarily dependent upon concentrative nucleoside transporters (CNTs). Analysis of lysates from an ImmH-resistant CCRF-CEM-AraC-8D cells demonstrated undetectable deoxycytidine kinase (dCK) activity, suggesting that dCK and not deoxyguanosine kinase (dGK) was the rate-limiting enzyme for phosphorylation of dGuo in these cells. Examination of ImmH cytotoxicity in a hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient cell line CCRF-CEM-AraC-8C, demonstrated enhanced sensitivity to low concentrations of ImmH and dGuo. RT-PCR and sequencing of HGPRT from the HGPRT-deficient CCRF-CEM-AraC-8C cells identified an Exon 8 deletion mutation in this enzyme. Thus these studies show that specific nucleoside transporters are required for ImmH cytotoxicity and predict that ImmH may be more cytotoxic to 6-thioguanine (6-TG) or 6-thiopurine-resistant leukemia cells caused by HGPRT deficiency.

Huang, Min; Wang, Yanhong; Gu, Jingjin; Yang, Jing; Noel, Karen; Mitchell, Beverly S.; Schramm, Vern L.; Graves, Lee M.

2008-01-01

277

[p21(WAF1) Gene Transfection Inhibits Proliferation of Leukemia Cell Line K562  

PubMed

To explore the functional role of p21(WAF1) gene on the proliferation of leukemia cell line K562, a p21(WAF1) retroviral expression vector was constructed. Mediated by FuGENE trade mark 6, p21(WAF1) was transfected into leukemia cell line K562, which was without p21(WAF1) expression. After selected in G418, K562 cell clones that expressed p21(WAF1) stabaly were isolated and named K562-p21(WAF1). The ectopic expression of p21(WAF1) mRNA and protein in K562 cells was identified by RT-PCR and Western Blot. The cell proliferaton was tested in liquid and soft agar culture after transfection. The cell cycle was tested by FCM. The expression of p21(WAF1) protein and mRNA could be detected in K562-p21(WAF1) cells. A strong inhibition of cell proliferation was observed in K562-p21(WAF1) cell clones cultured in liquid media as well as soft agar (P < 0.01). The cell number in G(0)/G(1) phase was remarkably increased. The findings showed that p21(WAF1) can inhibit the proliferation of leukemia cells, and it could be a potential target gene for leukemia gene therapy. PMID:12578615

Yang, Hui; Wang, Shen-Wu; Yin, Hui-Jun

2001-06-01

278

Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia  

PubMed Central

More than 70% of patients survive childhood leukemia, but chemotherapy and radiation therapy cause irreversible impairment of spermatogenesis. Although autotransplantation of germ cells holds promise for restoring fertility, contamination by leukemic cells may induce relapse. In this study, we isolated germ cells from leukemic mice by FACS sorting. The cell population in the high forward-scatter and low side-scatter regions of dissociated testicular cells from leukemic mice were analyzed by staining for MHC class I heavy chain (H-2Kb/H-2Db) and for CD45. Cells that did not stain positively for H-2Kb/H-2Db and CD45 were sorted as the germ cell–enriched fraction. The sorted germ cell–enriched fractions were transplanted into the testes of recipient mice exposed to alkylating agents. Transplanted germ cells colonized, and recipient mice survived. Normal progeny were produced by intracytoplasmic injection of sperm obtained from recipient testes. When unsorted germ cells from leukemic mice were transplanted into recipient testes, all recipient mice developed leukemia. The successful birth of offspring from recipient mice without transmission of leukemia to the recipients indicates the potential of autotransplantation of germ cells sorted by FACS to treat infertility secondary to anticancer treatment for childhood leukemia.

Fujita, Kazutoshi; Ohta, Hiroshi; Tsujimura, Akira; Takao, Tetsuya; Miyagawa, Yasushi; Takada, Shingo; Matsumiya, Kiyomi; Wakayama, Teruhiko; Okuyama, Akihiko

2005-01-01

279

Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells  

PubMed Central

There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing and other industries. Epidemiological studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on formaldehyde’s ability to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse impact on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures.

Zhang, Luoping; Tang, Xiaojiang; Rothman, Nathaniel; Vermeulen, Roel; Ji, Zhiying; Shen, Min; Qiu, Chuangyi; Guo, Weihong; Liu, Songwang; Reiss, Boris; Laura Beane, Freeman; Ge, Yichen; Hubbard, Alan E.; Hua, Ming; Blair, Aaron; Galvan, Noe; Ruan, Xiaolin; Alter, Blanche P.; Xin, Kerry X.; Li, Senhua; Moore, Lee E.; Kim, Sungkyoon; Xie, Yuxuan; Hayes, Richard B.; Azuma, Mariko; Hauptmann, Michael; Xiong, Jun; Stewart, Patricia; Li, Laiyu; Rappaport, Stephen M.; Huang, Hanlin; Fraumeni, Joseph F.; Smith, Martyn T.; Lan, Qing

2010-01-01

280

Bortezomib suppresses the growth of leukemia cells with Notch1 overexpression in vivo and in vitro.  

PubMed

Bortezomib has been widely used in the treatment of various cancers; however, its exact mechanisms of action are not fully understood, particularly in acute T lymphoblast leukemia (T-ALL). Here, we visualize the anti-leukemia effect of bortezomib in both human T-ALL cell line and animal models. In vitro study, a human T-ALL cell line bearing Notch1 mutations, MOLT-4, was treated with bortezomib. At clinically achievable concentrations, bortezomib inhibited cell growth by inducing G1 phase arrest and apoptosis with a dose-dependent manner. A murine tumor xenograft model was achieved by subcutaneous injection of MOLT-4 cells for in vivo study. Administration of bortezomib significantly reduced tumor mass volume when compared with controls. Of note, bortezomib inhibited growth of leukemia cells in a Notch1-induced murine T-ALL model, and the life span of leukemia-bearing mice was markedly increased. Further studies revealed that bortezomib led to inhibited expression of Notch1 target genes. Taken together, our results demonstrate that bortezomib shows significant anti-leukemia effect in T-ALL bearing Notch1 mutations in vitro and in vivo. The present study provides evidence that bortezomib might be a candidate therapeutic reagent in the treatment of T-ALL. PMID:22996635

Huang, Chongmei; Hu, Xiaoxia; Wang, Libing; Lü, Shuqing; Cheng, Hui; Song, Xianmin; Wang, Jianmin; Yang, Jianmin

2012-09-21

281

Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia  

PubMed Central

Summary We characterized leukemia stem cells (LSC) in chronic phase chronic myelogenous leukemia (CML) using a transgenic mouse model. LSC were restricted to cells with long-term hematopoietic stem cell (LTHSC) phenotype. CML LTHSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. Altered cytokine expression in CML BM was associated with selective impairment of normal LTHSC growth and a growth advantage to CML LTHSC. Imatinib (IM) treatment partially corrected abnormalities in cytokine levels and LTHSC growth. These results were validated using human CML samples and provide improved understanding of microenvironmental regulation of normal and leukemic LTHSC and their response to IM in CML.

Zhang, Bin; Ho, Yin Wei; Huang, Qin; Maeda, Takahiro; Lin, Allen; Lee, Sung-uk; Hair, Alan; Holyoake, Tessa L.; Huettner, Claudia; Bhatia, Ravi

2012-01-01

282

Protective roles of epithelial cells in the survival of adult T-cell leukemia/lymphoma cells.  

PubMed

Adult T-cell leukemia/lymphoma (ATL) is a highly invasive and intractable T-cell malignancy caused by human T-cell leukemia virus-1 infection. We demonstrate herein that normal tissue-derived epithelial cells (NECs) exert protective effects on the survival of leukemic cells, which may partially account for high resistance to antileukemic therapies in patients with ATL. Viral gene-silenced, ATL-derived cell lines (ATL cells) dramatically escaped from histone deacetylase inhibitor-induced apoptosis by direct co-culture with NECs. Adhesions to NECs suppressed p21(Cip1) expression and increased a proportion of resting G0/G1 phase cells in trichostatin A (TSA)-treated ATL cells. ATL cells adhering to NECs down-regulated CD25 expression and enhanced vimentin expression, suggesting that most ATL cells acquired a quiescent state by cell-cell interactions with NECs. ATL cells adhering to NECs displayed highly elevated expression of the cancer stem cell marker CD44. Blockade of CD44 signaling diminished the NEC-conferred resistance of ATL cells to TSA-induced apoptosis. Co-culture with NECs also suppressed the expression of NKG2D ligands on TSA-treated ATL cells, resulting in decreased natural killer cell-mediated cytotoxicity. Combined evidence suggests that interactions with normal epithelial cells augment the resistance of ATL cells to TSA-induced apoptosis and facilitate immune evasion by ATL cells. PMID:23474084

Miyatake, Yukiko; Oliveira, André L A; Jarboui, Mohamed Ali; Ota, Shuichi; Tomaru, Utano; Teshima, Takanori; Hall, William W; Kasahara, Masanori

2013-03-06

283

Congenital hairy polyp of the soft palate.  

PubMed

Hairy polyp is an unusual developmental malformation that is most frequently seen as a pedunculated tumor in the neonate. They are benign lesions containing elements of both ectodermal and mesodermal origin. The symptoms of hairy polyps relate both to their location and their size. Larger lesions produce symptoms due to feeding difficulties and airway obstruction while smaller lesions cause intermittent symptoms resulting from a ball-valve type of obstruction. We present two cases of a soft palate hairy polyp causing respiratory and feeding difficulties and review the literature. PMID:22078743

Yilmaz, Mehmet; Ibrahimov, Metin; Ozturk, Ozcan; Karaman, Emin; Aslan, Mehmet

2011-11-09

284

Treatment of Aggressive NK-Cell Leukemia: A Case Report and Review of the Literature  

PubMed Central

Aggressive NK-cell leukemia is a rare malignancy with neoplastic proliferation of natural killer cells. It often presents with constitutional symptoms, a rapid declining clinical course, and a poor prognosis with a median survival of a few months. The disease is usually resistant to cytotoxic agents, and no treatment has emerged as the standard of care for these patients. We report a case of an 18-year-old male who obtains complete remission following two lines of combination chemotherapy. We describe in details our regimens for induction chemotherapy and perform a review of existing literature concerning treatment of aggressive NK-cell leukemia.

Boysen, Anders Kindberg; Jensen, Paw; Johansen, Preben; Dybkaer, Karen; Nyegaard, Mette

2011-01-01

285

Induction of death of leukemia cells by TW-74, a novel derivative of chloro-naphthoquinone.  

PubMed

We have previously shown that a 2-chloro-1,4-naphthoquinone derivative (TW-92) induces cell death in leukemia cells. TW-92 exhibited relatively high selectivity towards primary Acute Myeloid Leukemia (AML) cells, as compared to normal mononuclear cells. In view of the selectivity of this family of naphthoquinones, novel chloroaminophenylnaphthoquinone isomers with different methyl substitutions on the phenyl ring were synthesized, and their effect on leukemia cells was tested. These compounds induced cell death in U937 human myeloid leukemia cells, which was prominent following 48 h of culture. Structure-activity relationship studies revealed that TW-74, a novel chloronaphthoquinone with a methyl group at the meta (m) position, was the most active derivative in inducing apoptosis. The mechanism underlying cell death induction by TW-74 was further investigated in U937 cells, a monocytic cell line which serves as a sensitive model of apoptosis induction. TW-74 induced rapid activation of Mitogen Activated Protein Kinases (MAPKs). It caused swelling of isolated rat liver mitochondria and an early reduction of mitochondrial membrane potential in intact cells, indicative of a direct effect on mitochondria. Apoptosis induced by TW-74 was accompanied by cytochrome C release and caspase activation. TW-74 induced down- regulation of (BCL2), an anti-apoptotic protein. Furthermore, TW-74 induced selective dose-dependent cell death in primary B-Chronic Lymphocytic Leukemia (CLL) cells. These findings demonstrate that chloronaphthoquiniones use common as well as diverse mechanisms for the induction of cell death. The data reported here warrant further studies of the utility of TW-74 in the treatment of CLL. PMID:23267144

Hallak, Maher; Thakur, Basant K; Winn, Thida; Shpilberg, Ofer; Bittner, Shmuel; Granot, Yosef; Levy, Itai; Nathan, Ilana

2013-01-01

286

Enhancement of fludarabine sensitivity by all-trans-retinoic acid in chronic lymphocytic leukemia cells  

PubMed Central

Background A subset of patients with fludarabine-resistant chronic lymphocytic leukemia has previously been shown to express elevated intracellular levels of the concentrative high-affinity fludarabine transporter hCNT3, without any detectable related activity. We have recently shown that all-trans-retinoic acid is capable of inducing hCNT3 trafficking to plasma membrane in the MEC1 cell line. We, therefore, evaluated the effect of all-trans-retinoic acid on hCNT3 in primary chronic lymphocytic leukemia cells as a suitable mechanism to improve fludarabine-based therapy of chronic lymphocytic leukemia. Design and Methods Cells from 23 chronic lymphocytic leukemia patients wild-type for P53 were analyzed for ex vivo sensitivity to fludarabine. hCNT3 activity in chronic lymphocytic leukemia cell samples was evaluated by measuring the uptake of [8-3H]-fludarabine. The amounts of transforming growth factor-?1 and hCNT3 messenger RNA were analyzed by real-time polymerase chain reaction. The effect of all-trans-retinoic acid on hCNT3 subcellular localization was analyzed by confocal microscopy and its effect on fludarabine-induced apoptosis was evaluated by flow cytometry analysis using annexin V staining. Results Chronic lymphocytic leukemia cases showing higher ex vivo basal sensitivity to fludarabine also had a greater basal hCNT3-associated fludarabine uptake capacity compared to the subset of patients showing ex vivo resistance to the drug. hCNT3 transporter activity in chronic lymphocytic leukemia cells from the latter patients was either negligible or absent. Treatment of the fludarabine-resistant subset of chronic lymphocytic leukemia cells with all-trans-retinoic acid induced increased fludarabine transport via hCNT3 which was associated with a significant increase in fludarabine sensitivity. Conclusions Improvement of ex vivo fludarabine sensitivity in chronic lymphocytic leukemia cells is associated with increased hCNT3 activity after all-trans-retinoic acid treatment.

Fernandez-Calotti, Paula X.; Lopez-Guerra, Monica; Colomer, Dolors; Pastor-Anglada, Marcal

2012-01-01

287

Apoptosis of B-cell chronic lymphocytic leukemia cells induced by a novel BH3 peptidomimetic.  

PubMed

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in human adults of the Western world and no definitive cure is yet available. The disease is characterized by accumulation of clonal malignant B lymphocytes resistant to apoptosis. Strategies to hit the anti-apoptotic drift of the Bcl-2 family in B-CLL cells are being explored. A novel peptidomimetic based on the BH3 domain of the pro-apoptotic protein Bim and recently shown to exert significant apoptotic activity on acute myeloid leukemia cells, both in vitro and in vivo, was assayed on ex-vivo derived leukemic cells from untreated B-CLL patients (n = 7). We found that this peptide, named 072RB, induced apoptosis of B-CLL samples at a concentration that does not affect viability of peripheral and bone marrow derived lymphocytes from healthy donors. Apoptosis was demonstrated by activation of Bak and Bax, externalization of plasma membranes phosphadydilserines, appearance of hypodiploid events in DNA flow cytometry histograms and was accompanied by dissipation of the mitochondrial transmembrane potential. Before the onset of marked apoptotic signs a progressive decline of the relevant anti-apoptotic proteins Bcl-X(L) and Mcl-1 could be observed. The negative control peptide 072RBL94A was ineffective for B-CLL cells, supporting the sequence specificity of 072RB activity. No relationship was found between responsiveness to 072RB and Mcl-1/Bcl-X(L) basal levels or decrease magnitude, possibly because of the limited sample size of the study. Altogether, we demonstrate that 072RB induces significant apoptosis of B-CLL cells subsequent to Bcl-X(L) and Mcl-1 downregulation. PMID:19164937

Ghiotto, Fabio; Fais, Franco; Tenca, Claudya; Tomati, Valeria; Morabito, Fortunato; Casciaro, Salvatore; Mumot, Anna; Zoppoli, Gabriele; Ciccone, Ermanno; Parodi, Silvio; Bruno, Silvia

2009-02-17

288

Multilevel targeting of hematopoietic stem cell self-renewal, differentiation and apoptosis for leukemia therapy.  

PubMed

Human leukemias are considered clonal hematological malignancies initiated by chromosomal aberrations or epigenetic alterations occurring at the level of either pluripotent hematopoietic stem cells (HSCs) or early multipotent progenitors (MPPs). Leukemic cells are transformed, immortalized, actively proliferating cells that are still able to differentiate into cells resembling mature blood cells. Future therapies of leukemias require identification of molecular targets involved in hematopoiesis under normal and leukemic conditions and detailed understanding of the interactions between normal hematopoietic and leukemic cells within the bone marrow micro-environment. This review presents the basic aspects of hematopoiesis and highlights multilevel exploitable targets for leukemia therapy. These include HSC niche components, signaling pathways (SCF/c-kit-R, EPO-R-JAK2/STAT, Wnt, Notch, HOX), inducer-receptor interactions, superfine chromatin structure modifications, fused transcription factors, microRNAs and signaling of cell death through the Bcl-2 apoptotic switch (BH3-only proteins). The classes of therapeutics developed or being under development to eradicate human leukemias include novel antimetabolites, DNA hypomethylating agents, histone deacetylation inhibitors (HDACIs), retinoids and other inducers of differentiation, targeted monoclonal antibodies raised against cell surface proteins, pro-apoptotic receptor agonists (PARAs), BH3 peptidomimetics, cell cycle inhibitors, siRNAs and perhaps microRNAs. Some of these agents induce terminal differentiation while others promote cell cycle arrest and apoptosis in leukemia cells. At last but not least, this article describes the mechanisms of removal of damaged/harmful cells from organs since impairment in clearance of such cells can lead to autoimmune disorders by self-antigens. PMID:19306896

Tsiftsoglou, Asterios S; Bonovolias, Ioannis D; Tsiftsoglou, Stefanos A

2009-03-21

289

Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors  

PubMed Central

Understanding the heterogeneous genetic mechanisms of tumor initiation in lymphoid leukemias (LL) will lead to improvements in prognostic classification and treatment regimens. In previous studies of mouse leukemias, we showed that retroviral insertion at the Evi32 locus leads to increased expression of Prdm14, a pluripotency gene implicated in the self-renewal capacity of embryonic stem cells and the early stages of breast cancer. Here we show that PRDM14 is also overexpressed in ~25% of human lymphoid neoplasms, with increased frequencies in T-cell acute LL (T-ALL) and hyperdiploid precursor B-cell acute LL (pre-B ALL). To test if Prdm14 overexpression could initiate leukemia, mice were transduced with bone marrow (BM) cells transfected with a Prdm14 expression vector. Lymphoid leukemias developed in 96% of female mice and 42% of male mice. Prior to the onset of leukemia, differentiation of transduced cells was biased up to 1000-fold towards cells with features of common lymphoid progenitors (CLP), and lymphoid differentiation showed a relative block at the pro-B stage. Microarray gene expression analysis of expanded CLP-like cells prior to the onset of leukemia demonstrated upregulation of genes involved in pluripotency, tumor initiation, early B-lineage commitment, Wnt/Ras signaling, and the epithelial-to-mesenchymal transition. Among the dysregulated genes were imprinted genes and non-coding RNAs including Dlk1 and Meg3, which are also key pluripotency mediators. Heightened expression of the estrogen-dependent oncogene, Myb, in tumors suggests a basis for the increased frequency of cancer in female mice. These data provide the first direct evidence for the association of Prdm14 with cancer initiation in an in vivo mouse model and in human lymphoid malignancies, while suggesting mechanisms for Prdm14’s mode of action.

Dettman, E.J.; Simko, Stephen J.; Ayanga, Bernard; Carofino, Brandi; Margolin, Judith; Morse, Herbert C.; Justice, Monica J.

2011-01-01

290

Leukemia mortality by cell type in petroleum workers with potential exposure to benzene.  

PubMed Central

Workers in the petroleum industry are potentially exposed to a variety of petrochemicals, including benzene or benzene-containing liquids. Although a large number of studies of petroleum workers have been conducted to examine leukemia and other cancer risks, few existing studies have investigated cell-type-specific leukemias. One of the major reasons for the lack of cell-type-specific analysis was the small number of deaths by cell type in individual studies. In the present investigation, all cohort studies of petroleum workers in the United States and the United Kingdom were combined into a single database for cell-type-specific leukemia analysis. The majority of these workers were petroleum refinery employees, but production, pipeline, and distribution workers in the petroleum industry were also included. The combined cohort consisted of more than 208,000 petroleum workers, who contributed more than 4.6 million person-years of observation. Based on a meta-analysis of the combined data, cell-type-specific leukemia risks were expressed in terms of standardized mortality ratios (meta-SMRs). The meta-SMR for acute myeloid leukemia was 0.96. The lack of an increase of acute myeloid leukemia was attributed to the low levels of benzene exposure in the petroleum industry, particularly in comparison to benzene exposure levels in some previous studies of workers in other industries, who had been found to experience an increased risk of acute myeloid leukemia. Similarly, no increase in chronic myeloid, acute lymphocytic, or chronic lymphocytic leukemias was found in petroleum workers (meta-SMRs of 0.89, 1.16, and 0.84, respectively). Stratified meta-analyses restricted to refinery studies or to studies with at least 15 years of follow-up yielded similar results. The findings of the present investigation are consistent with those from several recent case-control studies of cell-type-specific leukemia. Patterns and levels of benzene exposure in the petroleum industry are reviewed. The results of the present epidemiologic investigation are discussed in conjunction with recent advances in leukemogenesis from other scientific disciplines.

Raabe, G K; Wong, O

1996-01-01

291

Apigenin decreases cell viability and telomerase activity in human leukemia cell lines.  

PubMed

Recent studies have shown that apigenin (4',5,7-trihydroxyflavone inhibits human malignant cancer cell growth through cell cycle arrest and apoptosis. However, the underlying relationship between apoptosis and telomerase activity in response to apigenin exposure is not well understood. In this study, we found that apigenin significantly induces direct cytotoxicity in human leukemia cells (U937, THP-1 and HL60) through activation of the caspase pathway. As we presumed, treatment with apigenin was found to increase the level of intracellular reactive oxygen species (ROS), whereas pretreatment with antioxidants, N-acetyl-cysteine (NAC) or glutathione (GSH), completely attenuated ROS generation. Surprisingly, these antioxidants did not promote recuperation from apigenin-induced cell death. We further showed that apigenin downregulates telomerase activity in caspase-dependent apoptosis and observed that apigenin dosing results in downregulation of telomerase activity by suppression of c-Myc-mediated telomerase reverse transcriptase (hTERT) expression. In addition, treatment of apigenin-dosed cells with the two antioxidants did not restore telomerase activity. Taken together, this data suggests that ROS is not essential for suppression of apigenin-mediated apoptosis associated with the activation of caspases and regulation of telomerase activity via suppression of hTERT. We conclude that apigenin has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells. PMID:22617349

Jayasooriya, R G P T; Kang, Sang-Hyuck; Kang, Chang-Hee; Choi, Yung Hyun; Moon, Dong-Oh; Hyun, Jin-Won; Chang, Weon-Young; Kim, Gi-Young

2012-05-19

292

Effect of Mongolian Medicinal Plant Stellera Chamaejasme on Chronic Leukemia Cells K562  

Microsoft Academic Search

\\u000a Programmed cell death comprises apoptosis which is manifested by caspases activations and subsequent nuclear fragmentation.\\u000a Recently the cell’s suicide program has been found to involve autophagic compartment. In this study we report that ethanol\\u000a extract of Mongolian medicinal plant Stellera chamaejasme induced autophagy in chronic leukemia cell line K562. The cells were treated with 0.002–0.5% of the extract for 24,

Soninkhishig Tsolmon; Parida Yamada; Hiroko Isoda

293

Glucocorticoid Sensitivity and Receptors in Cells of HumanMyelogenous Leukemia Line  

Microsoft Academic Search

cells are ASD-chboroacetateestenase positive, and the line retainsthe samekaryotypic abnormalitythat was present in the fresh leukemia cells of the patient. The HL-60 cell line was derivedfrom a patient with promyebocyticleukemia.Thesecells are predominantly at the pnomyebocyte stage of development and stain positive for peroxidase and ASD-chboroacetatees terase. The cells retain the karyotype of the fresh beukemic cells and are abbeto produce

H. Phillip Koeffber; David W. Golde; Marc E. Lippman

294

Membrane-bound IgE receptor complexes fused with rat basophilic leukemia cells mediate degranulation  

Microsoft Academic Search

The high affinity receptor for IgE on rat basophilic leukemia (RBL) cells mediates antigen- triggered cellular degranulation. Polyethylene glycol- induced membrane fusion methods were used to in- troduce exogenous IgE receptors into living RBL cells, and these were tested for normal activities. In cell- cell fusion experiments, RBL cells with fluorescein- labeled rat IgE bound to receptors and containing (5-1,2-3H(N))hydroxytryptamine

Katherine Estes; Laura L. Monfalcone; Stephen R. Hammes; David Holowka; Barbara Baird

1987-01-01

295

Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells  

SciTech Connect

Arsenic trioxide (As{sub 2}O{sub 3}) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As{sub 2}O{sub 3} affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As{sub 2}O{sub 3} to induce a complete remission in relapsed APL patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As{sub 2}O{sub 3} exposure in leukemia cells.

Sumi, Daigo, E-mail: sdaigo@ph.bunri-u.ac.j [Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180, Yamashiro-cho, Tokushima-city, Tokushima 770-8514 (Japan); Shinkai, Yasuhiro; Kumagai, Yoshito [Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

2010-05-01

296

Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods  

Microsoft Academic Search

Adult patients with acute leukemia have, in general, a poor prognosis, with long-term, disease-free survival achieved in only approximately one-third of cases. One of the proposed mechanisms for this poor overall response is the inability of the immune system to detect and eliminate residual malignant leukemia cells, which subsequently serve as a source of leukemic relapse. This review discusses the

R Stripecke; AM Levine; V Pullarkat; AA Cardoso

2002-01-01

297

Selected Epidemiological Observations of Cell-Specific Leukemia Mortality in the USA, 1969-1977.  

National Technical Information Service (NTIS)

Utilizing a newly available data set which includes for the first time cell-specific leukemia mortality rates for the USA during the period 1969-1977, age and sex distributions, time trends and geographic patterns have been analyzed. Four major cell types...

S. Selvin L. I. Levin D. W. Merrill W. Winkelstein

1982-01-01

298

Induction of apoptosis in acute lymphoblastic leukemia cells by isolated fractions from strawberries  

Technology Transfer Automated Retrieval System (TEKTRAN)

Strawberries contain phytochemicals that have anti-inflammatory and anti-cancer activity. We investigated the ability of isolated fractions from strawberry extracts to induce apoptotic cell death in three pre-B acute lymphoblastic leukemia (ALL) lines, including SEM and RS4;11 cell lines derived fr...

299

A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia  

Microsoft Academic Search

The hematopoietic stem cell underlying acute myeloid leukemia (AML) is contro- versial. Flow cytometry and the DNA- binding dye Hoechst 33342 were previ- ously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and patho-

Gerald G. Wulf; Rui-Yu Wang; Ingrid Kuehnle; Douglas Weidner; Frank Marini; Malcolm K. Brenner; Michael Andreeff; Margaret A. Goodell

2001-01-01

300

Leukemogenicity and cell transformation mechanisms in vitro by Gross murine leukemia virus: analysis of virus subpopulations.  

PubMed Central

The leukemogenic activity of Gross murine leukemia virus adapted to rats was tested in W/Fu rats and NIH/Swiss mice. All animals infected with this virus developed thymic and nonthymic T-cell leukemia with a short latency period. It was observed that cell-free extracts from thymic lymphoma tissue of mice and rats, induced by either Gross murine leukemia virus or Gross murine leukemia virus adapted to rats, consisted of both small-plaque-forming and large-plaque-forming viruses, as determined by the XC plaque test. MCF-type virus was found in these virus complexes. Transformed cell foci were induced in SC-1 cell layers by double infection of the cloned MCF-type virus and an ecotropic virus. SC-1 cells containing transformed cell foci were shown to be tumorigenic upon inoculation into nude mice. The formation of transformed cell foci in mink lung cells was also observed after double infection with the cloned MCF-type virus and a xenotropic virus. The possible mechanism of leukemogenesis by endogenous viruses is discussed. Images

Hamada, K; Yanagihara, K; Kamiya, K; Seyama, T; Yokoro, K

1981-01-01

301

Toona sinensis extracts induces apoptosis via reactive oxygen species in human premyelocytic leukemia cells  

Microsoft Academic Search

Toona sinensis (T. sinensis), well known in Taiwan as a traditional Chinese medicine, has been shown to exhibit antioxidant effects. In this study, therefore, the ability of T. sinensis to induce apoptosis was studied in cultured human premyelocytic leukemia HL-60 cells. Treatment of the HL-60 cells with a variety of concentrations of the aqueous extracts of T. sinensis (TS extracts)

Hsin-Ling Yang; Wen-Huei Chang; Yi-Chen Chia; Chin-Jung Huang; Fung-Jou Lu; Hseng-Kuang Hsu; You-Cheng Hseu

2006-01-01

302

Lymphoblastoid Cell Lines from Patients with Chronic Lymphocytic Leukemia: Identification of Tumor Origin by Idiotypic Analysis  

Microsoft Academic Search

Multiple lymphoblastoid cell lines have been derived from two patients with chronic lymphocytic leukemia with an associated monoclonal immunoglobulin (Ig) band. Idiotypic antisera raised against the monoclonal serum Ig bands were shown to be specific for the membrane Ig of the patients' leukemic cells. The idiotypic determinants in these patients thereby constitute tumor-specific antigens. Surface and intracellular immunofluorescence studies utilizing

John N. Hurley; Shu Man Fu; Henry G. Kunkel; Gillies McKenna; Matthew D. Scharff

1978-01-01

303

High Throughput Algorithm for Leukemia Cell Population Statistics on a Hemocytometer  

Microsoft Academic Search

This paper presents a high throughput cell count and cluster classification algorithm to quantify population statistics of leukemia cell lines on a conventional hemocytometer. The algorithm has been designed, implemented and tested on test images that vary in image quality. The proposed algorithm uses a recursively segmented, median filtered and a boosted Prewitt gradient mask to generate a boundary box

Brinda Prasad; Wael Badawy

2007-01-01

304

Induction of Differentiation in Human Promyelocytic Leukemia Cells by Tumor Promoters  

Microsoft Academic Search

Phorbol diester tumor promoters and the promoter mezerein convert human promyelocytic leukemia cells in culture into adherent, nonproliferating cells with many of the characteristics of macrophages. Other types of promoters such as anthralin, phenobarbital, and saccharin do not have this effect. Various compounds that can inhibit some of the biological and biochemical effects of tumor promoters do not interfere with

Giovanni Rovera; Thomas G. O'Brien; Leila Diamond

1979-01-01

305

Functional but Abnormal Adult Erythropoiesis in the Absence of the Stem Cell Leukemia Gene  

Microsoft Academic Search

Previous studies have indicated that the stem cell leukemia gene (SCL) is essential for both embryonic and adult erythropoiesis. We have examined erythropoiesis in conditional SCL knockout mice for at least 6 months after loss of SCL function and report that SCL was important but not essential for the generation of mature red blood cells. Although SCL-deleted mice were mildly

Mark A. Hall; Nicholas J. Slater; C. Glenn Begley; Jessica M. Salmon; Leonie J. Van Stekelenburg; Matthew P. McCormack; Stephen M. Jane; David J. Curtis

2005-01-01

306

Hyperaccumulation of cadmium by hairy roots of Thlaspi caerulescens  

SciTech Connect

Hairy roots were used to investigate cadmium uptake by Thlaspi caerulescens, a metal hyperaccumulator plant with potential applications in phytoremediation and phytomining. Experiments were carried out in nutrient media under conditions supporting root growth. Accumulation of Cd in short-term (9-h) experiments varied with initial medium pH and increased after treating the roots with H{sup +}-ATPase inhibitor. The highest equilibrium Cd content measured in T. caerulescens roots was 62,800 {micro}g g{sup {minus}1} dry weight, or 6.3% dry weight, at a liquid Cd concentration of 3,710 ppm. Cd levels in live T. caerulescens roots were 1.5- to 1.7-fold those in hairy roots of nonhyperaccumulator species exposed to the same Cd concentration, but similar to the Cd content of auto-claved T. caerulescens roots. The ability to grow at Cd concentrations of up to 100 ppm clearly distinguished T. caerulescens hairy roots from the nonhyperaccumulators. The specific growth rate of T. caerulescens roots was essentially unaffected by 20 to 50 ppm Cd in the culture medium; in contrast, N. tabacum roots turned dark brown at 20 ppm and growth was negligible. Up to 10,600 {micro}g g{sup {minus}1} dry weight Cd was accumulated by growing T. caerulescens hairy roots. Measurement of Cd levels in while roots and in the cell wall fraction revealed significant differences in the responses of T. caerulescens and N. tabacum roots to 20 ppm Cd. Most metal was transported directly into the symplasm of N. tabacum roots within 3 days of exposure; in contrast, T. caerulescens roots stored virtually all of their Cd in the wall fraction for the first 7 to 10 days. This delay in transmembrane uptake may represent an important defensive strategy against Cd poisoning in T. caerulescens, allowing time for activation of intracellular mechanisms for heavy metal detoxification.

Nedelkoska, T.V.; Doran, P.M.

2000-03-05

307

Attempt to Immunize Guinea Pigs Against Leukemia by Skin Scarification with Leukemic Cell Suspensions  

PubMed Central

An attempt was made to immunize “strain 2” guinea pigs by superficial skin scarification with small doses of L2C leukemic cell suspensions. Among 203 scarified guinea pigs, 32 developed progressively growing leukemic tumors at the site of skin scarification. In 35 guinea pigs small intradermal tumors that appeared at the site of scarification regressed spontaneously; however, 15 guinea pigs in which the intradermal tumor regressed later developed generalized leukemia. In addition, 13 other animals developed generalized leukemia, without an apparent local tumor formation at the site of scarification. A total of 60 out of 203 scarified guinea pigs (30%) died from leukemia. 143 Guinea pigs that survived the scarification were challenged by subcutaneous inoculation of massive doses (0.5 ml each of a 10-fold dilution from a 10% extract) of leukemic cell extracts and only 48 (34%) developed leukemia; 95 guinea pigs (66%) resisted the challenge and remained in good health. In a control experiment, 156 untreated “strain 2” guinea pigs were inoculated subcutaneously (0.5 ml each) with L2C leukemic cell suspensions of 10-2 or 10-3 dilution, and all but two (99%) developed generalized leukemia. Images

Gross, Ludwik

1973-01-01

308

Sugar-Binding Activity of Pea Lectin Expressed in White Clover Hairy Roots.  

PubMed Central

Introduction of the pea (Pisum sativum L.) lectin (PSL) gene into white clover (Trifolium repens L.) hairy roots facilitates nodulation by the nitrogen-fixing bacterium Rhizobium leguminosarum biovar viciae, which normally nodulates pea and not white clover (C.L. Diaz, L.S. Melchers, P.J.J. Hooykaas, B.J.J. Lugtenberg, and J.W. Kijne [1989] Nature 338: 579-581). Here, we show that PSL is functionally expressed in transgenic white clover hairy roots transformed with the PSL gene. PSL could be isolated from these roots by affinity chromatography. Immunoanalysis of PSL showed the presence of polypeptides corresponding to the PSL precursor and its [beta] subunits. In addition, we developed a highly sensitive localization technique based on specific binding of a glycan moiety of rat IgE to PSL. Similar to the situation in pea roots, PSL appeared to be localized on the external cell surface of elongated epidermal cells and on the tips of emerging and growing root hairs of transgenic white clover hairy roots. PSL was not observed on normal white clover roots and on hairy roots without the PSL gene. These results show that (a) in transgenic white clover hairy roots, PSL is correctly processed and targeted to root cells susceptible to rhizobial infection, and (b) like in pea roots, PSL is surface bound with at least one of its two sugar-binding sites available for (rhizobial) ligands.

Diaz, C. L.; Logman, TJJ.; Stam, H. C.; Kijne, J. W.

1995-01-01

309

Mutation of the NPM1 gene contributes to the development of donor cell-derived acute myeloid leukemia after unrelated cord blood transplantation for acute lymphoblastic leukemia.  

PubMed

Donor cell leukemia (DCL) is a rare but severe complication after allogeneic stem cell transplantation. Its true incidence is unknown because of a lack of correct recognition and reporting, although improvements in molecular analysis of donor-host chimerism are contributing to a better diagnosis of this complication. The mechanisms of leukemogenesis are unclear, and multiple factors can contribute to the development of DCL. In recent years, cord blood has emerged as an alternative source of hematopoietic progenitor cells, and at least 12 cases of DCL have been reported after unrelated cord blood transplantation. We report a new case of DCL after unrelated cord blood transplantation in a 44-year-old woman diagnosed as having acute lymphoblastic leukemia with t(1;19) that developed acute myeloid leukemia with normal karyotype and nucleophosmin (NPM1) mutation in donor cells. To our knowledge, this is the first report of NPM1 mutation contributing to DCL development. PMID:23465275

Rodríguez-Macías, Gabriela; Martínez-Laperche, Carolina; Gayoso, Jorge; Noriega, Víctor; Serrano, David; Balsalobre, Pascual; Muñoz-Martínez, Cristina; Díez-Martín, José L; Buño, Ismael

2013-03-01

310

Resveratrol Induces Extensive Apoptosis by Depolarizing Mitochondrial Membranes and Activating Caspase9 in Acute Lymphoblastic Leukemia Cells1  

Microsoft Academic Search

Resveratrol, a plant antibiotic, has been found to have anticancer activity and was recently reported to induce apoptosis in the myeloid leukemia line HL60 by the CD95-CD95 ligand pathway. However, many acute lymphoblastic leukemias (ALLs), particularly of B-lineage, are re- sistant to CD95-mediated apoptosis. Using leukemia lines derived from patients with pro-B t(4;11), pre-B, and T-cell ALL, we show in

Jan Dorrie; Harald Gerauer; Yvonne Wachter; Susan J. Zunino

2001-01-01

311

Modeling T-cell acute lymphoblastic leukemia induced by the SCL and LMO1 oncogenes.  

PubMed

Deciphering molecular events required for full transformation of normal cells into cancer cells remains a challenge. In T-cell acute lymphoblastic leukemia (T-ALL), the genes encoding the TAL1/SCL and LMO1/2 transcription factors are recurring targets of chromosomal translocations, whereas NOTCH1 is activated in >50% of samples. Here we show that the SCL and LMO1 oncogenes collaborate to expand primitive thymocyte progenitors and inhibit later stages of differentiation. Together with pre-T-cell antigen receptor (pre-TCR) signaling, these oncogenes provide a favorable context for the acquisition of activating Notch1 mutations and the emergence of self-renewing leukemia-initiating cells in T-ALL. All tumor cells harness identical and specific Notch1 mutations and Tcrbeta clonal signature, indicative of clonal dominance and concurring with the observation that Notch1 gain of function confers a selective advantage to SCL-LMO1 transgenic thymocytes. Accordingly, a hyperactive Notch1 allele accelerates leukemia onset induced by SCL-LMO1 and bypasses the requirement for pre-TCR signaling. Finally, the time to leukemia induced by the three transgenes corresponds to the time required for clonal expansion from a single leukemic stem cell, suggesting that SCL, LMO1, and Notch1 gain of function, together with an active pre-TCR, might represent the minimum set of complementing events for the transformation of susceptible thymocytes. PMID:20516195

Tremblay, Mathieu; Tremblay, Cédric S; Herblot, Sabine; Aplan, Peter D; Hébert, Josée; Perreault, Claude; Hoang, Trang

2010-06-01

312

Modeling T-cell acute lymphoblastic leukemia induced by the SCL and LMO1 oncogenes  

PubMed Central

Deciphering molecular events required for full transformation of normal cells into cancer cells remains a challenge. In T-cell acute lymphoblastic leukemia (T-ALL), the genes encoding the TAL1/SCL and LMO1/2 transcription factors are recurring targets of chromosomal translocations, whereas NOTCH1 is activated in >50% of samples. Here we show that the SCL and LMO1 oncogenes collaborate to expand primitive thymocyte progenitors and inhibit later stages of differentiation. Together with pre-T-cell antigen receptor (pre-TCR) signaling, these oncogenes provide a favorable context for the acquisition of activating Notch1 mutations and the emergence of self-renewing leukemia-initiating cells in T-ALL. All tumor cells harness identical and specific Notch1 mutations and Tcr? clonal signature, indicative of clonal dominance and concurring with the observation that Notch1 gain of function confers a selective advantage to SCL-LMO1 transgenic thymocytes. Accordingly, a hyperactive Notch1 allele accelerates leukemia onset induced by SCL-LMO1 and bypasses the requirement for pre-TCR signaling. Finally, the time to leukemia induced by the three transgenes corresponds to the time required for clonal expansion from a single leukemic stem cell, suggesting that SCL, LMO1, and Notch1 gain of function, together with an active pre-TCR, might represent the minimum set of complementing events for the transformation of susceptible thymocytes.

Tremblay, Mathieu; Tremblay, Cedric S.; Herblot, Sabine; Aplan, Peter D.; Hebert, Josee; Perreault, Claude; Hoang, Trang

2010-01-01

313

Expression analysis of homeobox genes in leukemia/lymphoma cell lines.  

PubMed

Homeobox genes code for transcription factors which have a strong impact on cellular behavior, including differentiation, proliferation, and survival. Therefore, upon deregulation these genes may turn into oncogenes, contributing substantially to cancerogenesis. Among hematopoietic malignancies, including leukemias and lymphomas, several homeo-oncogenes have been described. Many of them have been identified in hematopoietic cell lines, which serve as useful tools for oncogene hunting and characterization. Here, we describe molecular methods for analysis and quantification of dysregulated homeobox gene expression in leukemia/lymphoma cell lines. PMID:21516422

Nagel, Stefan; Drexler, Hans G

2011-01-01

314

Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells  

PubMed Central

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as “subset 1”) recognize antigens highly expressed in stromal cells – vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20–45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease.

Binder, Mascha; Lechenne, Barbara; Ummanni, Ramesh; Scharf, Christan; Balabanov, Stefan; Trusch, Maria; Schluter, Hartmut; Braren, Ingke; Spillner, Edzard; Trepel, Martin

2010-01-01

315

Aberrant B cell receptor signaling from B29 (Ig, CD79b) gene mutations of chronic lymphocytic leukemia B cells  

Microsoft Academic Search

Chronic lymphocytic leukemia (CLL) B cells characteristically exhibit low or undetectable surface B cell receptor (BCR) and diminished responses to BCR-mediated signaling. These features suggest that CLL cells may have sustained mutations affecting one or more of the BCR proteins required for receptor surface assembly and signal transduction. Loss of expression and mutations in the critical BCR protein B29 (Ig,

Melinda S. Gordon; Roberta M. Kato; Frederick Lansigan; Alexis A. Thompson; Randolph Wall; David J. Rawlings

2000-01-01

316

Increased cell proliferation, but not reduced cell death, induces lymphocytosis in bovine leukemia virus-infected sheep  

Microsoft Academic Search

Lymphocyte homeostasis is the result of a critical balance between cell proliferation and death. Disruption of this subtle equilibrium can lead to the onset of leukemia, an increase in the number of lymphocytes being potentially due to both of these parameters. The relative importance of cell proliferation vs. apoptosis during pathogenesis induced by the primate T cell lymphotropic viruses and

Christophe Debacq; Becca Asquith; Pierre Kerkhofs; Daniel Portetelle; Arsène Burny; Richard Kettmann; Luc Willems

2002-01-01

317

Effect of dietary polyphenols on K562 leukemia cells: a Foodomics approach.  

PubMed

In this work, a global Foodomics strategy has been applied to study the antiproliferative effect of dietary polyphenols from rosemary on two human leukemia lines, one showing a drug-sensitive phenotype (K562), and another exhibiting a drug-resistant phenotype (K562/R). To this aim, whole-transcriptome microarray together with an MS-based nontargeted analytical approach (via CE-TOF MS and UPLC-TOF MS) have been employed to carry out transcriptomics and metabolomics analyses, respectively. Functional enrichment analysis was done using ingenuity pathway analysis (IPA) software as a previous step for a reliable interpretation of transcriptomic and metabolomic profiles. Rosemary polyphenols altered the expression of approximately 1% of the genes covered by the whole transcriptome microarray in both leukemia cell lines. Overall, differences in the transcriptional induction of a number of genes encoding phase II detoxifying and antioxidant genes, as well as differences in the metabolic profiles observed in the two leukemia cell lines suggest that rosemary polyphenols may exert a differential chemopreventive effect in leukemia cells with different phenotypes. IPA predictions on transcription factor analysis highlighted inhibition of Myc transcription factor function by rosemary polyphenols, which may explain the observed antiproliferative effect of rosemary extract in the leukemia cells. Metabolomics analysis suggested that rosemary polyphenols affected differently the intracellular levels of some metabolites in two leukemia cell sublines. Integration of data obtained from transcriptomics and metabolomics platforms was attempted by overlaying datasets on canonical (defined) metabolic pathways using IPA software. This strategy enabled the identification of several differentially expressed genes in the metabolic pathways modulated by rosemary polyphenols providing more evidences on the effect of these compounds. PMID:22887152

Valdés, Alberto; Simó, Carolina; Ibáñez, Clara; Rocamora-Reverte, Lourdes; Ferragut, José Antonio; García-Cañas, Virginia; Cifuentes, Alejandro

2012-08-01

318

DC-SIGN Facilitates Fusion of Dendritic Cells with Human T-Cell Leukemia Virus Type 1Infected Cells  

Microsoft Academic Search

Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced syncy- tium formation. DC-SIGN is known to bind

Pierre-Emmanuel Ceccaldi; Frederic Delebecque; Marie-Christine Prevost; Arnaud Moris; Jean-Pierre Abastado; Antoine Gessain; Olivier Schwartz; Simona Ozden

2006-01-01

319

[Effect of cucurmosin on chronic myeloid leukemia k562 cell line].  

PubMed

This study was aimed to investigate the antitumor effect of pumpkin protein (cucurmosin, CUS) on subcutaneous transplant tumor in chronic myeloid leukemia K562 cell-NOD/SCID mice and leukemia model. The subcutaneous transplant tumor in K562-NOD/SCID mice and leukemia model were established; using two models, the antitumor activity of CUS in mice was evaluated. The results indicated that the inhibitory rate of 0.5 mg/kg and 1 mg/kg CUS on subcutaneous transplant tumor were 53.45% and 59.43% respectively; survival time of mice received 0.25 mg/kg and 0.5 mg/kg CUS was 39.8 ± 5.5 d and 43.4 ± 6.6 d, antitumor rate was 24.9% and 36% respectively. It is concluded that CUS has significant inhibitory effect on mice with CML cell line K562. PMID:23998580

Liu, Ting-Bo; Liu, Hui-Li; Xie, Jie-Ming; Hu, Jian-Da

2013-07-01

320

Membrane potential changes during IgE-mediated histamine release from rat basophilic leukemia cells  

Microsoft Academic Search

Summary The membrane potential of rat basophilic leukemia cells (RBL-2H3 cell line) has been determined by monitoring the distribution of the lipophilic [3H] tetraphenylphosphonium cation between the cells and the extracellular medium. By this method, the determined potential of these cells, passively sensitized with IgE, is ?93±5 mV (mean±sem, interior negative). Almost 40% of this membrane potential is rapidly collapsed

Ronit Sagi-Eisenberg; Israel Pecht

1983-01-01

321

Human T-Cell Leukemia Virus Type 1 Tax Dysregulates  -Catenin Signaling  

Microsoft Academic Search

Dysregulation of -catenin signaling has been implicated in the malignant transformation of cells. However, the role of -catenin in the human T-cell leukemia virus type 1 (HTLV-1)-induced transformation of T cells is unknown. Here we found that -catenin protein was overexpressed in the nucleus and that -catenin-dependent transcription was significantly enhanced in Tax-positive HTLV-1-infected T-cell lines compared to that in

Mariko Tomita; Akira Kikuchi; Tetsu Akiyama; Yuetsu Tanaka; Naoki Mori

2006-01-01

322

Boswellic acid acetate induces apoptosis through caspase-mediated pathways in myeloid leukemia cells.  

PubMed

The mechanism of the cytotoxic effect of boswellic acid acetate, a 1:1 mixture of alpha-boswellic acid acetate and beta-boswellic acid acetate, isolated from Boswellia carterri Birdw on myeloid leukemia cells was investigated in six human myeloid leukemia cell lines (NB4, SKNO-1, K562, U937, ML-1, and HL-60 cells). Morphologic and DNA fragmentation assays indicated that the cytotoxic effect of boswellic acid acetate was mediated by induction of apoptosis. More than 50% of the cells underwent apoptosis after treatment with 20 mug/mL boswellic acid for 24 hours. This apoptotic process was p53 independent. The levels of apoptosis-related proteins Bcl-2, Bax, and Bcl-XL were not modulated by boswellic acid acetate. Boswellic acid acetate induced Bid cleavage and decreased mitochondrial membrane potential without production of hydrogen peroxide. A general caspase inhibitor (Z-VAD-FMK) and a specific caspase-8 inhibitor II (Z-IETD-FMK) blocked boswellic acid acetate-induced apoptosis. The mRNAs of death receptors 4 and 5 (DR4 and DR5) were induced in leukemia cells undergoing apoptosis after boswellic acid acetate treatment. These data taken together suggest that boswellic acid acetate induces myeloid leukemia cell apoptosis through activation of caspase-8 by induced expression of DR4 and DR5, and that the activated caspase-8 either directly activates caspase-3 by cleavage or indirectly by cleaving Bid, which in turn decreases mitochondria membrane potential. PMID:15767547

Xia, Lijuan; Chen, Duo; Han, Rui; Fang, Qicheng; Waxman, Samuel; Jing, Yongkui

2005-03-01

323

Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells.  

PubMed

Vascular endothelial growth factor-A, an angiogenesis stimulator expressed on both tumor endothelial and malignant T cells, is involved in tumor progression in T-leukemia/lymphoma. Here, we assessed the impact of therapeutic vascular endothelial growth factor-A blockade on tumor-endothelial cell interaction and on tumor progression. In a murine xenograft T-leukemia/lymphoma model, combined bevacizumab (monoclonal antibody against vascular endothelial growth factor-A) with doxorubicin, compared with doxorubicin alone, significantly delayed tumor growth and induced prevalence of tumor cell apoptosis over mitosis. More importantly, the combined treatment induced endothelial cell swelling, microvessel occlusions, and tumor necrosis. In vitro, co-culture of endothelial cells with T-leukemia/lymphoma cells showed that doxorubicin induced expression of intracellular cell adhesion molecule-1, provided endothelial and malignant T cells were in direct contact. This was abrogated by bevacizumab treatment with doxorubicin. Taken together, bevacizumab enhances the chemotherapeutic effect on T-leukemia/lymphoma cells. Directly targeting tumor endothelial cells might be a promising therapeutic strategy to counteract tumor progression in T-cell malignancies. PMID:21330328

Wang, Li; Shi, Wen-Yu; Yang, Fan; Tang, Wei; Gapihan, Guillaume; Varna, Mariana; Shen, Zhi-Xiang; Chen, Sai-Juan; Leboeuf, Christophe; Janin, Anne; Zhao, Wei-Li

2011-02-17

324

Bevacizumab potentiates chemotherapeutic effect on T-leukemia/lymphoma cells by direct action on tumor endothelial cells  

PubMed Central

Vascular endothelial growth factor-A, an angiogenesis stimulator expressed on both tumor endothelial and malignant T cells, is involved in tumor progression in T-leukemia/lymphoma. Here, we assessed the impact of therapeutic vascular endothelial growth factor-A blockade on tumor-endothelial cell interaction and on tumor progression. In a murine xenograft T-leukemia/lymphoma model, combined bevacizumab (monoclonal antibody against vascular endothelial growth factor-A) with doxorubicin, compared with doxorubicin alone, significantly delayed tumor growth and induced prevalence of tumor cell apoptosis over mitosis. More importantly, the combined treatment induced endothelial cell swelling, microvessel occlusions, and tumor necrosis. In vitro, co-culture of endothelial cells with T-leukemia/lymphoma cells showed that doxorubicin induced expression of intracellular cell adhesion molecule-1, provided endothelial and malignant T cells were in direct contact. This was abrogated by bevacizumab treatment with doxorubicin. Taken together, bevacizumab enhances the chemotherapeutic effect on T-leukemia/lymphoma cells. Directly targeting tumor endothelial cells might be a promising therapeutic strategy to counteract tumor progression in T-cell malignancies.

Wang, Li; Shi, Wen-Yu; Yang, Fan; Tang, Wei; Gapihan, Guillaume; Varna, Mariana; Shen, Zhi-Xiang; Chen, Sai-Juan; Leboeuf, Christophe; Janin, Anne; Zhao, Wei-Li

2011-01-01

325

Targeting fusion protein/corepressor contact restores differentiation response in leukemia cells  

PubMed Central

The AML1/ETO and PML/RAR? leukemia fusion proteins induce acute myeloid leukemia by acting as transcriptional repressors. They interact with corepressors, such as N-CoR and SMRT, that recruit a multiprotein complex containing histone deacetylases on crucial myeloid differentiation genes. This leads to gene repression contributing to generate a differentiation block. We expressed in leukemia cells containing PML/RAR? and AML1/ETO N-CoR protein fragments derived from fusion protein/corepressor interaction surfaces. This blocks N-CoR/SMRT binding by these fusion proteins, and disrupts the repressor protein complex. In consequence, the expression of genes repressed by these fusion proteins increases and differentiation response to vitamin D3 and retinoic acid is restored in previously resistant cells. The alteration of PML/RAR?–N-CoR/SMRT connections triggers proteasomal degradation of the fusion protein. The N-CoR fragments are biologically effective also when directly transduced by virtue of a protein transduction domain. Our data indicate that fusion protein activity is permanently required to maintain the leukemia phenotype and show the route to developing a novel therapeutic approach for leukemia, based on its molecular pathogenesis.

Racanicchi, Serena; Maccherani, Chiara; Liberatore, Concetta; Billi, Monia; Gelmetti, Vania; Panigada, Maddalena; Rizzo, Giovanni; Nervi, Clara; Grignani, Francesco

2005-01-01

326

The Hairiness of Worsted Wool and Cashmere Yarns and the Impact of Fibre Curvature on Hairiness  

Microsoft Academic Search

In this study, a range of carefully selected wool and cashmere yarns as well as their blends were used to examine the effects of fibre curvature and blend ratio on yarn hairiness. The results indicate that yarns spun from wool fibres with a higher curvature have lower yarn hairiness than yarns spun from similar wool of a lower curvature. For

Xungai Wang; Lingli Chang; Bruce McGregor

327

Allogeneic hematopoietic stem cell transplantation for patients with acute leukemia  

PubMed Central

Objective The purposes of this study were to assess the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia (AL) and analyze the factors affecting the prognosis of these patients. Methods The clinical and follow-up data of 93 AL patients (median age, 30 years) undergoing allogeneic HSCT in Xiangya Hospital over the past 12 years were collected, and the potential factors affecting the efficacy and prognosis of allogeneic HSCT patients were determined. Results Hematopoietic reconstitution was achieved in 90 patients. At the last follow-up, the incidences of severe acute graft versus host disease (aGvHD) and extensive chronic GvHD (cGvHD) were 14.0% and 20.0%, the 3-year cumulative incidence of transplantation related mortality (TRM) and relapse rate were 16.8%±6.1% and 21.3%±6.7%, and the estimated 3-year overall survival (OS) and disease-free survival (DFS) of the patients were 64.6%±5.4% and 56.5%±5.5%, respectively. Univariate analysis indicated that age older than 40 years, HLA mismatch, and severe lung infection within the first 100 days after transplantation were risk factors for severe aGvHD, age older than 40 years, HLA mismatch, severe lung infection within the first 100 days after transplantation, and severe aGvHD were risk factors for TRM, high-risk AL and lack of cGvHD were risk factors for relapse (all P<0.05). Survival estimation showed that HLA mismatch, severe lung infection occurring within the first 100 days post-transplantation, high-risk AL severe aGvHD and lack of cGvHD were risk factors associated with poor prognosis (all P<0.05). Further multivariate analyses revealed that severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD were independent risk factors for unfavorable outcomes (all P<0.05). Conclusions Allogeneic HSCT can improve the DFS of AL patients, and severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD are independent risk factors affecting the prognosis.

Xu, Yajing; Fu, Gan; Liu, Yi; Peng, Jie; Fu, Bin; Yuan, Xiaoyu; Xin, Hongya; Zhu, Yan; He, Qun; Wu, Dengshu; Shu, Yigang; Li, Xiaolin; Zhao, Xielan; Chen, Fangping

2013-01-01

328

The AF4-mimetic peptide, PFWT, induces necrotic cell death in MV4-11 leukemia cells  

PubMed Central

Despite ongoing success in the treatment of childhood acute lymphoblastic leukemia, patients harboring translocations involving the MLL gene at chromosome 11q23 remain resistant to treatment. To improve outcomes, novel therapeutics designed to target the unusual biology of these leukemias need to be developed. Previously, we identified an interaction between the two most common MLL fusion proteins, AF4 and AF9, and designed a synthetic peptide (PFWT) capable of disrupting this interaction. PFWT induced cell death in leukemia cells expressing MLL-AF4 with little effect on the colony forming potential of hematopoietic progenitor cells, suggesting the AF4–AF9 complex is an important pharmacological target for leukemia therapy and PFWT is a promising chemotherapeutic prototype. In these studies, we demonstrate that PFWT induces death by necrosis in MV4-11 cells. Cell death is characterized by rapid loss of plasma membrane integrity with maintenance of nuclear membrane integrity, and is independent of caspase activation, DNA fragmentation, and mitochondrial membrane depolarization. PFWT-mediated necrosis is inhibited by the serine protease inhibitor TLCK, suggesting this death pathway is regulated. Given the resistance of t(4;11) leukemias to conventional chemotherapeutic agents that induce apoptosis, further identification of the molecular events mediating this death process should uncover new avenues for therapeutic intervention.

Palermo, Christine M.; Bennett, Cecily A.; Winters, Amanda C.; Hemenway, Charles S.

2008-01-01

329

Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice  

SciTech Connect

The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

1980-07-01

330

Clonal analysis of childhood acute lymphoblastic leukemia with "cytogenetically independent" cell populations.  

PubMed Central

Acute lymphoblastic leukemia (ALL) is generally regarded as a clonal disease in which a single abnormal progenitor cell gives rise to neoplastic progeny. Five of 463 cases of childhood ALL with adequately banded leukemic cells were found to have two cytogenetically independent cell populations. In addition, two of the four cases tested had more than two rearranged immunoglobulin genes and (or) T cell receptor genes. To investigate the clonality of these unusual leukemias, we examined the neoplastic cells for X-linked markers extrinsic to the disease. Leukemic cells from each of the three patients heterozygous for an X-linked, restriction fragment length polymorphism showed a single active parental allele, suggesting that both apparently independent cell populations developed from a common progenitor. These cases provide evidence that leukemogenesis involves a multistep process of mutation and suggest that karyotypic abnormalities may be a late event of malignant transformation. Images

Pui, C H; Raskind, W H; Kitchingman, G R; Raimondi, S C; Behm, F G; Murphy, S B; Crist, W M; Fialkow, P J; Williams, D L

1989-01-01

331

Transplantation of transduced nonhuman primate CD34+ cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells  

Microsoft Academic Search

The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34+ cells and colony- forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34+ cells

B A Bunnell; K A Kluge; S-Q Lee-Lin; E R Byrne; D Orlic; M E Metzger; B A Agricola; R P Wersto; D M Bodine; R A Morgan; R E Donahue

1999-01-01

332

[Inhibition of B cell receptor signaling: a first targeted therapeutic approach for chronic lymphocytic leukemia and other B cell lymphomas].  

PubMed

Chronic lymphocytic leukemia (CLL) is the most frequent, yet by conventional therapy still incurable, leukemia in the Western world. Accumulating evidence of the role of B ?cell receptor (BCR) pathway in CLL B ?cell bio-logy suggests the possible use of BCR inhibitors for targeted therapy. Recently published results of clinical trials of three different molecules (fosfamatinib, ibrutinib and GS?1101) targeting BCRassociated kinases (Syk, Btk, PI3K) showed impressive clinical activity in CLL. These findings will likely modify treatment approaches for chronic lymphocytic leukemia and some other B ?cell lymphomas in the near future. Herein, we review the data on BCR pathway deregulation in malignant CLL B ?cells, and the results of clinical trials utilizing fosfamatinib, ibrutinib and GS?1101. PMID:23763320

M, Mráz; Doubek, M; Mayer, J

2013-01-01

333

Differentiation of Chronic Lymphocytic Leukemia B Cells into Immunoglobulin Secreting Cells Decreases LEF-1 Expression  

PubMed Central

Lymphocyte enhancer binding factor 1 (LEF-1) plays a crucial role in B lineage development and is only expressed in B cell precursors as B cell differentiation into mature B and plasma cells silences its expression. Chronic lymphocytic leukemia (CLL) cells aberrantly express LEF-1 and its expression is required for cellular survival. We hypothesized that modification of the differentiation status of CLL cells would result in loss of LEF-1 expression and eliminate the survival advantage provided by its aberrant expression. In this study, we first established a methodology that induces CLL cells to differentiate into immunoglobulin (Ig) secreting cells (ISC) using the TLR9 agonist, CpG, together with cytokines (CpG/c). CpG/c stimulation resulted in dramatic CLL cell phenotypic and morphologic changes, expression of cytoplasmic Ig, and secretion of light chain restricted Ig. CpG/c stimulation also resulted in decreased CLL cell LEF-1 expression and increased Blimp-1 expression, which is crucial for plasma cell differentiation. Further, Wnt pathway activation and cellular survival were impaired in differentiated CLL cells compared to undifferentiated CLL cells. These data support the notion that CLL can differentiate into ISC and that this triggers decreased leukemic cell survival secondary to the down regulation of LEF-1 and decreased Wnt pathway activation.

Gutierrez, Albert; Arendt, Bonnie K.; Tschumper, Renee C.; Kay, Neil E.; Zent, Clive S.; Jelinek, Diane F.

2011-01-01

334

Prevalence of human herpesvirus 8 DNA in peripheral blood mononuclear cells of acute and chronic leukemia patients in Taiwan.  

PubMed

Human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma and several other human malignancies. The prevalence of HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) in Taiwanese leukemia populations has not been investigated. In this study, HHV-8 DNA was extracted from PBMCs, and detected in 10.29% of the leukemia cases and 8.94% of the relatives' cases. In addition, the prevalence of HHV-8 DNA in PBMCs was nonsignificantly associated with gender, age and leukemia subtypes. The study examines the prevalence of HHV-8 DNA in PBMCs in Taiwanese leukemia and can be applied in further epidemiological studies. PMID:21392127

Chen, Chao-Hsien; Chang, Chun-Pin; Wu, Fang-Yan; Liu, Chao-Li; Peng, Ching-Tien; Lin, Cheng-Wen

2011-01-18

335

Organosilicon compounds as adult T-cell leukemia cell proliferation inhibitors.  

PubMed

Aggressive forms of adult T-cell leukemia (ATL) respond poorly to conventional anticancer chemotherapy, and new lead compounds are required for the development of drugs to treat this fatal disease. Recently, we developed ATL cell-selective proliferation inhibitors based on a tetrahydrotetramethylnaphthalene (TMN) skeleton 1, and here we report the design and synthesis of silicon analogs of TMN derivatives. Among them, compound 13 showed the most potent growth-inhibitory activity towards the ATL cell line S1T, though its selectivity for S1T over the non-ATL cell line MOLT-4 was only moderate. This result, as well as computational studies, suggests that sila-substitution (C/Si exchange) is useful for structure optimization of these inhibitors. PMID:23370198

Nakamura, Masaharu; Matsumoto, Yotaro; Toyama, Masaaki; Baba, Masanori; Hashimoto, Yuichi

2013-01-01

336

STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients.  

PubMed

A signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis. PMID:8634413

Gouilleux-Gruart, V; Gouilleux, F; Desaint, C; Claisse, J F; Capiod, J C; Delobel, J; Weber-Nordt, R; Dusanter-Fourt, I; Dreyfus, F; Groner, B; Prin, L

1996-03-01

337

Combination of celecoxib and doxorubicin increases growth inhibition and apoptosis in acute myeloid leukemia cells.  

PubMed

Abstract Cyclooxygenase-2 (COX-2) inhibitors have been shown to enhance antitumor activity of therapeutic agents in a variety of solid tumor cells. However, this has not been well established in hematopoietic tumors, especially in acute myeloid leukemia (AML). This study was designed to investigate the effects of the combination of celecoxib, a specific COX-2 inhibitor, and doxorubicin on cell growth and apoptosis in human leukemia cells. Co-treatment with celecoxib and doxorubicin significantly inhibited cell growth and induced cell apoptosis in the acute leukemia cell line HL60 and primary AML cells. The growth inhibition effect was accompanied by down-regulation of the expression of cyclin E and cyclin-dependent kinase 2 (CDK2), the key regulators of cell cycle progression, which was associated with arrest of cells at G0/G1 phase. The pro-apoptotic effect was accompanied by down-regulation of the expression of survivin, an inhibitor of apoptosis protein, which mediated anti-apoptosis in AML cells. These results provide the first evidence that the growth inhibitory and pro-apoptotic effects of celecoxib and doxorubicin on AML cells are synergistic. PMID:23452119

Chen, Chen; Xu, Wei; Wang, Cheng-Mei

2013-04-08

338

CD34(+) /CD38(-) acute myelogenous leukemia cells aberrantly express Aurora kinase A.  

PubMed

We previously showed that Aurora kinase A (AURKA) is aberrantly expressed in acute myelogenous leukemia (AML) cells when compared to bone marrow mononuclear cells isolated from healthy volunteers. We have also shown that CD34(+) /CD38(-) AML cells, one of compartments enriched for leukemia stem cells in most leukemia subgroups, were relatively resistant to cytarabine-mediated growth inhibition when compared to their CD34(+) /CD38(+) counterparts. Our study attempted to identify therapeutic targets in CD34(+) /CD38(-) AML cells and found that CD34(+) /CD38(-) AML cells isolated from patients (n?=?26) expressed larger amounts of AURKA than their CD34(+) /CD38(+) counterparts and CD34(+) normal hematopoietic stem/progenitor cells isolated from healthy volunteers (n?=?6), as measured by real-time reverse-transcriptase polymerase chain reaction. Blockade of AURKA by the specific inhibitor MLN8237 or a short hairpin RNA (shRNA) against AURKA significantly inhibited proliferation, impaired self-renewal capability and induced apoptosis of CD34(+) /CD38(-) AML cells, in association with modulation of levels of Bcl-2 family member proteins. Importantly, inhibition of AURKA in CD34(+) /CD38(-) AML cells by MLN8237 or an shRNA significantly impaired engraftment of these cells in severely immunocompromised mice and appeared to prolong their survival. These results suggest that AURKA is a promising molecular target to eliminate chemotherapy-resistant CD34(+) /CD38(-) AML cells. PMID:23686525

Yang, Jing; Ikezoe, Takayuki; Nishioka, Chie; Nobumoto, Atsuya; Udaka, Keiko; Yokoyama, Akihito

2013-06-10

339

Genetically Engineered Lymphocyte Therapy in Treating Patients With B-Cell Leukemia or Lymphoma That is Resistant or Refractory to Chemotherapy  

ClinicalTrials.gov

Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

2012-12-19

340

Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors.  

PubMed

Understanding the heterogeneous genetic mechanisms of tumor initiation in lymphoid leukemias (LL) will lead to improvements in prognostic classification and treatment regimens. In previous studies of mouse leukemias, we showed that retroviral insertion at the ecotropic viral insertion site 32 locus leads to increased expression of Prdm14, a pluripotency gene implicated in the self-renewal capacity of embryonic stem cells and the early stages of breast cancer. Here, we show that PRDM14 is also overexpressed in ?25% of human lymphoid neoplasms, with increased frequencies in T-cell acute LL and hyperdiploid precursor B-cell acute LL. To test if Prdm14 overexpression could initiate leukemia, mice were transduced with bone marrow cells transfected with a Prdm14 expression vector. LLs developed in 96% of female mice and 42% of male mice. Before the onset of leukemia, differentiation of transduced cells was biased up to 1000-fold toward cells with features of common lymphoid progenitors (CLPs), and lymphoid differentiation showed a relative block at the pro-B stage. Microarray gene expression analysis of expanded CLP-like cells before the onset of leukemia demonstrated upregulation of genes involved in pluripotency, tumor initiation, early B-lineage commitment, Wnt/Ras signaling and the epithelial-to-mesenchymal transition. Among the dysregulated genes were imprinted genes and non-coding RNAs including Dlk1 and Meg3, which are also key pluripotency mediators. Heightened expression of the estrogen-dependent oncogene, Myb, in tumors suggests a basis for the increased frequency of cancer in female mice. These data provide the first direct evidence for the association of Prdm14 with cancer initiation in an in vivo mouse model and in human lymphoid malignancies, while suggesting mechanisms for Prdm14's mode of action. PMID:21339739

Dettman, E J; Simko, S J; Ayanga, B; Carofino, B L; Margolin, J F; Morse, H C; Justice, M J

2011-02-21

341

Radiogenic leukemia revisited  

SciTech Connect

Radiation-induced leukemia is considered to be similar to the de novo disease. However, following an analysis of clinical and hematological findings in leukemia occurring in irradiated cervical cancer patients, adult Japanese atomic-bomb survivors, and spondylitics treated with x-ray, striking differences were noted. Acute leukemias in cervical cancer patients and Japanese survivors were similar in type to acute de novo leukemias in adults. Cell types among spondylitics were very dissimilar; rare forms, eg, acute erythromyelocytic leukemia (AEL) and acute megakaryocytic leukemia, were increased. Pancytopenia occurred in 25 of 35 cases and erythromyelodysplastic disorders were noted in seven of 35 acute cases. The leukemias and myelodysplastic disorders closely resembled those occurring in patients treated with alkylating agents. This similarity suggests a common pathogenesis involving marrow stem cell injury and extra-medullary mediators of hematopoiesis. Investigation of early acute leukemias and myelodysplastic disorders with newer techniques may provide valuable insights into the pathogenesis of leukemia in humans.

Moloney, W.C.

1987-10-01

342

Inhibition of growth of leukemia cells by enzymic folate depletion.  

PubMed

A new bacterial enzyme, designated as carboxypeptidase G(1), inhibited growth of the L5178Y and L1210 murine leukemias, as well as the Walker carcinoma and the human lymphoblastoid line (RPMI 4265), propogated in vitro. This enzyme hydrolyzes the glutamate moiety from both oxidized and reduced folate forms, and thus it may prove to be of value in creating rapid folate depletion in vivo. PMID:5313376

Bertino, J R; O'Brien, P; McCullough, J L

1971-04-01

343

NADPH-dependent reductases and polyol formation in human leukemia cell lines.  

PubMed

Because of the limited availability of human tissues, leukemia cell lines are often utilized as the models for human leukocytes. In this study, we investigated the NADPH-dependent reductases and polyol pathway in commonly utilized human leukemia cell lines. The relative amounts of aldose and aldehyde reductases were estimated by separating two enzymes with chromatofocusing. The flux of glucose through the polyol pathway was examined by 19F-NMR using 3-fluoro-3-deoxy-D-glucose (3FG) as substrate. Sugar alcohol analysis was conducted by gas chromatography. In myelocytic leukemia cells, the major reductase was aldehyde reductase, and levels of aldose reductase were extremely low. Although lymphocytic cells also contained both aldose and aldehyde reductases, the levels of aldose reductase appeared to be higher in lymphocytic cells than myeolcytic cells. In two lymphocytic cells MOLT-4 and SKW6.4, aldose reductase is clearly dominant. When incubated in medium containing D-galactose, all cell lines quickly accumulated galactitol. There was correlation between galactitol levels and aldose reductase levels. The aldose reductase inhibitor FK 366 significantly reduced the formation of galactitol. 19F-NMR of the cells cultured with 3FG as substrate demonstrated the formation of 3-fluoro-3-dexoy-sorbitol in all the cell lines examined in this study. The relative amounts of sorbitol and fructose varied significantly among the cells. The data confirm that the polyol pathway is present in both myelocytic and lymphocytic leukemia cell lines. However, there is a large variation among the cell lines in the levels of enzymes and flux of glucose through the polyol pathway. PMID:12604223

Sato, Sanai; Secchi, E Filippo; Sakurai, Shinichi; Ohta, Nobuo; Fukase, Shigeru; Lizak, Martin J

2003-02-01

344

High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival  

Microsoft Academic Search

PURPOSE: In CD34-positive acute myeloid leukemia (AML), the leukemia-initiating event originates from the CD34(+)CD38(-) stem cell compartment. Survival of these cells after chemotherapy may lead to minimal residual disease (MRD) and subsequently to relapse. Therefore, the prognostic impact of stem cell frequency in CD34-positive AML was investigated. EXPERIMENTAL DESIGN: First, the leukemogenic potential of unpurified CD34(+)CD38(-) cells, present among other

A. van Rhenen; N. Feller; A. Kelder; A. H. Westra; E. Rombouts; S. Zweegman; Pol van der M. A; Q. Waisfisz; G. J. Ossenkoppele; G. J. Schuurhuis

2005-01-01

345

Cold Spring Harbor's first comprehensive DNA study of mast cell leukemia uncovers clues that could improve therapy:  

Cancer.gov

Cancer researchers at Cold Spring Harbor Laboratory have carried out the first comprehensive study of the changes seen in the DNA of a patient with mast cell leukemia, an extremely aggressive subtype of acute myeloid leukemia with a very poor prognosis.

346

The Clinical Significance of Cytogenetic Studies in 100 Patients With Multiple Myeloma, Plasma Cell Leukemia, or Amy loidosis  

Microsoft Academic Search

earliest stages, may be recognized only as a monocbonal gammopathy of undetermined significance. They may slowly progress or become aggressive and evolve into overt plasma cell leukemia (PCL). In the early stages, observation is sufficient, but in the symptomatic stages, chemotherapy is needed. The situation is complicated by the fact that treat- ment-related leukemia may develop in some of the

Gordon W. Dewald; Robert A. Kyle; Gary A. Hicks; Philip R. Greipp

1985-01-01

347

Mobilization of CD34+CD38- hematopoietic stem cells after priming in acute myeloid leukemia  

PubMed Central

AIM: To evaluate quantitatively and qualitatively the different CD34+ cell subsets after priming by chemotherapy granulocyte colony-stimulating factor (± G-CSF) in patients with acute myeloid leukemia. METHODS: Peripheral blood and bone marrow samples were harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4 (CXCR4) (CD184), VLA-4 (CD49d/CD29) and CD47. RESULTS: Chemotherapy ± G-CSF mobilized immature cells (CD34+CD38? population), while the more mature cells (CD34+CD38low and CD34+CD38+ populations) decreased progressively after treatment. Circulating CD34+ cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34+ cell mobilization was correlated with a gradual increase in CXCR4 and CD47 expression, suggesting a role in cell protection and the capacity of homing back to the marrow. CONCLUSION: Chemotherapy ± G-CSF mobilizes into the circulation CD34+ bone marrow cells, of which, the immature CD34+CD38– cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients’ outcomes.

Plesa, Adriana; Chelghoum, Youcef; Mattei, Eve; Labussiere, Helene; Elhamri, Mohamed; Cannas, Giovanna; Morisset, Stephane; Tagoug, Ines; Michallet, Mauricette; Dumontet, Charles; Thomas, Xavier

2013-01-01

348

Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia  

PubMed Central

The malignant, CD5+ B lymphocytes of B cell chronic lymphocytic leukemia (B-CLL) die by apoptosis in vitro. This is in contrast to the prolonged life span of the leukemic cells in vivo and likely reflects the lack of essential growth factors in the tissue culture medium. We found that interferon gamma (IFN-gamma) inhibits programmed cell death and promotes survival of B-CLL cells in culture. This effect may also be important in vivo: increased serum levels of IFN-gamma, ranging from 60 to > 2,200 pg/ml, were found in 7 of 10 B-CLL samples tested, whereas the sera of 10 healthy individuals did not contain detectable levels of this cytokine (< 20 pg/ml). High levels of IFN-gamma message were detected in RNA from T cell-depleted B-CLL peripheral blood samples by Northern blot analysis. Synthesis of IFN-gamma by B-CLL lymphocytes was confirmed by in situ hybridization and flow cytometry. The majority of B-CLL cells (74-82%) expressed detectable levels of IFN- gamma mRNA, and CD19+ B-CLL cells were labeled with anti-IFN-gamma monoclonal antibodies. These results show that IFN-gamma inhibits programmed cell death in B-CLL cells and suggest that the malignant cells are able to synthesize this cytokine. By delaying apoptosis, IFN- gamma may extend the life span of the malignant cells and thereby contribute to their clonal accumulation.

1993-01-01

349

Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains  

PubMed Central

Epigenetic mechanisms regulating leukemia stem cells (LSCs) are an attractive target for therapy of blood cancers. Here, we report that conditional knockout of the DNA methyltransferase Dnmt1 blocked development of leukemia, and haploinsufficiency of Dnmt1 was sufficient to delay progression of leukemogenesis and impair LSC self-renewal without altering normal hematopoiesis. Haploinsufficiency of Dnmt1 resulted in tumor suppressor gene derepression associated with reduced DNA methylation and bivalent chromatin marks. These results suggest that LSCs depend on not only active expression of leukemogenic programs, but also DNA methylation-mediated silencing of bivalent domains to enforce transcriptional repression.

Trowbridge, Jennifer J.; Sinha, Amit U.; Zhu, Nan; Li, Mingjie; Armstrong, Scott A.; Orkin, Stuart H.

2012-01-01

350

Effect of allogeneic stem cell transplantation on bone marrow angiogenesis in chronic myelogenous leukemia  

Microsoft Academic Search

Increased bone marrow angiogenesis is a poor prognostic marker in patients with chronic myelogenous leukemia (CML). Allogeneic stem cell transplantation (ASCT) can be curative for patients with CML. Studies in myeloma have shown persistent increased bone marrow microvessel density (MVD) after autologous transplantation. It is not clear if abnormal bone marrow angiogenesis persists following a curative intervention like allogeneic transplantation.

S Kumar; M R Litzow; S V Rajkumar

2003-01-01

351

NYU study discovers new culprit in T-cell acute lymphoblastic leukemia:  

Cancer.gov

A new study published in the journal Nature Medicine by NYU Cancer Institute researchers, shows how the cancer causing gene Notch, in combination with a mutated Polycomb Repressive Complex 2 (PRC2) protein complex, work together to cause T- cell acute lymphoblastic leukemia (T-ALL).

352

Berberine inhibits arylamine N-acetyltransferase activity and gene expression in mouse leukemia L 1210 cells  

Microsoft Academic Search

N-acetyltransferases (NATs) are recognized to play a key role in the primary step of arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow acetylators, which are being thought to involve cancer risk related to environmental exposure. Berberine has been shown to induce apoptosis and affect NAT activity in human leukemia cells. The purpose of this study is to

S. S. Lin; J. G. Chung; J. P. Lin; J. Y. Chuang; W. C. Chang; J. Y. Wu; Y. S. Tyan

2005-01-01

353

Stem cell transplantation for chronic lymphocytic leukemia: should not more patients get a transplant?  

Microsoft Academic Search

Novel therapeutic approaches with conventional chemotherapy and monoclonal antibody combinations have improved the complete remission rates in chronic lymphocytic leukemia. However, cure remains elusive, particularly in fludarabine-refractory patients, whose prognosis remains poor. Autologous stem cell transplantation (SCT) has been explored for such patients, lengthening the time to treatment failure in selected patients, but there is little hope that it will

E Jabbour; M J Keating; R E Champlin; I F Khouri

2004-01-01

354

Signaling pathways activated by antigen-receptor engagement in chronic lymphocytic leukemia B-cells  

Microsoft Academic Search

Several features of the B-cell receptor (BCR) have emerged as major prognostic factors in chronic lymphocytic leukemia (CLL). In particular, the absence of somatic mutations in the immunoglobulin variable region genes and expression of the protein tyrosine kinase ZAP-70 are strongly associated with an aggressive clinical course, and both features have been correlated with a greater capacity of the BCR

Dimitar G. Efremov; Stefania Gobessi; Pablo G. Longo

2007-01-01

355

Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy  

Microsoft Academic Search

Natural-food-based compounds show substantial promise for prevention and biotherapy of cancers including leukemia. In general, their mechanism of action remains unclear, hampering rational use of these compounds. Herein we show that the common dietary flavonoid apigenin has anticancer activity, but also may decrease chemotherapy sensitivity, depending on the cell type. We analyzed the molecular consequences of apigenin treatment in two

R R Ruela-de-Sousa; G M Fuhler; N Blom; C V Ferreira; H Aoyama; M P Peppelenbosch

2010-01-01

356

T CELL RECEPTOR AND IMMUNOGLOBULIN GENE REARRANGEMENTS IN ACUTE MYELOBLASTIC LEUKEMIA  

Microsoft Academic Search

The nature of the blast cells in acute myeloblastic leukemia (AML) ~ has been examined extensively at the level of the phenotype. Morphology, using standard staining procedures such as Wright-Giemsa, is now supplemented with histochem- ical (1) or immunological methods (2-4) that detect markers associated with developmental stage or lineage. Morphological studies usually disclosed blasts that were homogeneous within each

GREGORY Y. CHENG; MARK D. MINDEN; BARRY TOYONAGA

1986-01-01

357

Investigating human leukemogenesis: from cell lines to in vivo models of human leukemia  

Microsoft Academic Search

The hematopoietic system produces appropriate levels of blood cells over an individual's lifetime through a careful balance of differentiation, proliferation and self-renewal. The acquisition of genetic and epigenetic alterations leads to deregulation of these processes and the development of acute leukemias. A prerequisite to targeted therapies directed against these malignancies is a thorough understanding of the processes that subvert the

J A Kennedy; F Barabé

2008-01-01

358

Emergence of Tumorigenic Cells during the Course of Friend Virus Leukemias  

Microsoft Academic Search

Appearance of tumorigenic cells was studied in DBA\\/2 and ICFW mice infected either with the polycythemia-inducing or the anemia-inducing strain of Friend leukemia virus. Tumorigenicity was defined by transplantability of virus-infected cells into the omentum of an isogeneic preirradiated host. Tumorigenic cells were detected in 50% of the leukemic donors 3 wk after infection by the polycythemia-inducing strain and 7-8

Francoise Wendling; Francoise Moreau-Gachelin; Pierre Tambourin

1981-01-01

359

Phenylbutyrate-induced G1 arrest and apoptosis in myeloid leukemia cells: structure–function analysis  

Microsoft Academic Search

The aromatic fatty acid phenylbutyrate (PB) induces cytostasis, differentiation, and apoptosis in primary myeloid leukemic cells at clinically achievable concentrations. In the present study, we have investigated the structural and cellular basis for PB-induced cytostasis, using the ML-1 human myeloid leukemia cell line as a model system. PB induced a dose-dependent increase in cells in G1 with a corresponding decrease

JA DiGiuseppe; L-J Weng; KH Yu; S Fu; MB Kastan; D Samid; SD Gore

1999-01-01

360

Primary plasma cell leukemia with extensive dense osteosclerosis: complete remission following combination chemotherapy  

Microsoft Academic Search

Diffuse osteosclerotic myeloma is very rare, and primary plasma cell leukemia with extensive osteosclerosis is even more rare. We describe a 71-year-old man who presented with severe anemia and dense widespread osteosclerosis similar to the X-ray finding of myelosclerosis. His peripheral blood showed 40% plasma cells. Bone marrow examination revealed heavy plasma cell infiltration with marked myelofibrosis and myelosclerosis. Protein

M.-C. Kuo; L.-Y. Shih

1995-01-01

361

Study of effects of Cordyceps sinensis on natural killer cells in leukemia  

Microsoft Academic Search

The effects ofCordyceps sinensis (CS) on peripheral natural killer cells from healthy subjects and from leukemia patients were studied. The results showed\\u000a CS could augment natural killer cell activity. The dose-dependent effect was found within the range of the dosage adopted\\u000a for the tests (r=0.984,PP16 marker expression on the surface of lymphocytes and the binding capacity of K562 cells. Cytotoxicity

Chao Liu; Shan Lu; Mei-rong Ji; Yi Xie

1995-01-01

362

Transduction of Human Hematopoietic Progenitor Cells with Retroviral Vectors Based on the Gibbon Ape Leukemia Virus  

Microsoft Academic Search

Gene transfer into human hematopoietic stem cells continues to be complicated by issues of transfer efficiency. We have examined the capacity of newly described retroviral vectors based on the gibbon ape leukemia virus (GaLV) to introduce genes into human hematopoietic progenitor cells. Total nucleated human bone marrow cells were transduced using GaLV vectors packaged with either amphotropic or GaLV envelopes.

Martin A. Eglitis; Richard D. Schneiderman

1997-01-01

363

T-cell prolymphocytic leukemia (T-PLL) with unique surface phenotype  

Microsoft Academic Search

Leukemic cells of a 19 year old patient with prolymphocytic leukemia of T-cell type (T-PLL) were characterized by surface markers and immunologic functions. Phenotypic analysis using a large panel of monoclonal antibodies corresponding to the clusters (CD) of differentiation antigens established on the leukocyte Typing Workshops I and II [1, 16] revealed a unique T-cell phenotype not yet reported in

Jtirgen Lohmeyer; Martin Hadam; Anthony Ho; Andreas Hesse; Hans Pralle

1987-01-01

364

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine  

PubMed Central

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m2, for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4×109/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment due to liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

Costa, Renata Oliveira; Bellesso, Marcelo; Chamone, Dalton Alencar Fischer; Ruiz, Milton Artur; Neto, Abrahao Elias Hallack; Aldred, Vera Lucia; Pereira, Juliana

2012-01-01

365

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 ...

366

[A quantitative assay for telomerase activity in peripheral blood mononuclear cells from patients with acute leukemia].  

PubMed

To establish a quantitative assay for telomerase activity and analyze the telomerase activity in peripheral blood mononuclear cells (PBMNC) from patients with acute leukemia, a fluorescent dye, PicoGreen, was added to the products after telomere repeat amplification protocol. The samples were excited at 480 nm and the fluorescence emission intensity was measured at 520 nm using a spectrofluorometer. Telomerase activity was detected in PBMNCs from 20 cases of normal individuals and 25 patients with acute leukemia. The results showed that the fluorescence of PicoGreen binding to double-stranded DNA specifically was enhanced with increase of DNA quantities. In conclusion, the met hod is rapid, simple and quantitative, the telomerase activities of PBMNCs from acute leukemia patients are significantly higher than that of the normal controls. PMID:12513783

Ma, Li-Ping; Pan, Xiu-Ying; Yan, Zhong-Yu; Zhang, Yan; Jiang, Bin; Wang, Shen-Wu

2002-06-01

367

Interferon and Cell Division, I. Inhibition of the Multiplication of Mouse Leukemia L 1210 Cells in vitro by Interferon Preparations  

Microsoft Academic Search

Mouse interferon preparations inhibited the multiplication of mouse leukemia L 1210 cells in stationary suspension cultures. The degree of inhibition was found to correlate with the antiviral titer of the interferon preparations. The factor(s) responsible for inhibition of L 1210 cell multiplication could not be dissociated from interferon by standard physicochemical means.

Ion Gresser; Daniele Brouty-Boye; Marie-Therese Thomas; Alvaro Macieira-Coelho

1970-01-01

368

High CD34 + cell dose promotes faster platelet recovery after autologous stem cell transplantation for acute myeloid leukemia  

Microsoft Academic Search

We studied platelet engraftment in 58 patients with acute myeloid leukemia in first remission treated with autologous stem cell transplantation (ASCT) to determine whether CD34+ cell doses >10 × 106\\/kg were associated with faster platelet engraftment. We compared engraftment rates in patients receiving CD34+ doses between 5 and 10 × 106\\/kg (standard-dose ASCT) with those receiving doses ?10 × 106\\/kg

Nathan Gunn; Lloyd Damon; Paul Varosy; Willis Navarro; Tom Martin; Curt Ries; Charles Linker

2003-01-01

369

Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells.  

PubMed

Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity. PMID:24104188

Tormoen, Garth W; Recht, Olivia; Gruber, András; Levine, Ross L; McCarty, Owen J T

2013-10-08

370

Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells  

NASA Astrophysics Data System (ADS)

Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.

Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.

2013-10-01

371

Epigenetic Inactivation of Notch-Hes Pathway in Human B-Cell Acute Lymphoblastic Leukemia  

PubMed Central

The Notch pathway can have both oncogenic and tumor suppressor roles, depending on cell context. For example, Notch signaling promotes T cell differentiation and is leukemogenic in T cells, whereas it inhibits early B cell differentiation and acts as a tumor suppressor in B cell leukemia where it induces growth arrest and apoptosis. The regulatory mechanisms that contribute to these opposing roles are not understood. Aberrant promoter DNA methylation and histone modifications are associated with silencing of tumor suppressor genes and have been implicated in leukemogenesis. Using methylated CpG island amplification (MCA)/DNA promoter microarray, we identified Notch3 and Hes5 as hypermethylated in human B cell acute lymphoblastic leukemia (ALL). We investigated the methylation status of other Notch pathway genes by bisulfite pyrosequencing. Notch3, JAG1, Hes2, Hes4 and Hes5 were frequently hypermethylated in B leukemia cell lines and primary B-ALL, in contrast to T-ALL cell lines and patient samples. Aberrant methylation of Notch3 and Hes5 in B-ALL was associated with gene silencing and was accompanied by decrease of H3K4 trimethylation and H3K9 acetylation and gain of H3K9 trimethylation and H3K27 trimethylation. 5-aza-2?-deoxycytidine treatment restored Hes5 expression and decreased promoter hypermethylation in most leukemia cell lines and primary B-ALL samples. Restoration of Hes5 expression by lentiviral transduction resulted in growth arrest and apoptosis in Hes5 negative B-ALL cells but not in Hes5 expressing T-ALL cells. These data suggest that epigenetic modifications are implicated in silencing of tumor suppressor of Notch/Hes pathway in B-ALL.

Kuang, Shao-Qing; Fang, Zhihong; Zweidler-McKay, Patrick A.; Yang, Hui; Wei, Yue; Gonzalez-Cervantes, Emilio A.; Boumber, Yanis; Garcia-Manero, Guillermo

2013-01-01

372

Reduced Cell Turnover in Bovine Leukemia Virus-Infected, Persistently Lymphocytotic Cattle  

PubMed Central

Although nucleotide analogs like bromodeoxyuridine have been extensively used to estimate cell proliferation in vivo, precise dynamic parameters are scarce essentially because of the lack of adequate mathematical models. Besides recent developments on T cell dynamics, the turnover rates of B lymphocytes are largely unknown particularly in the context of a virally induced pathological disorder. Here, we aim to resolve this issue by determining the rates of cell proliferation and death during the chronic stage of the bovine leukemia virus (BLV) infection, called bovine persistent lymphocytosis (PL). Our methodology is based on direct intravenous injection of bromodeoxyuridine in association with subsequent flow cytometry. By this in vivo approach, we show that the death rate of PL B lymphocytes is significantly reduced (average death rate, 0.057 day?1 versus 0.156 day?1 in the asymptomatic controls). Concomitantly, proliferation of the PL cells is also significantly restricted compared to the controls (average proliferation rate, 0.0046 day?1 versus 0.0085 day?1). We conclude that bovine PL is characterized by a decreased cell turnover resulting both from a reduction of cell death and an overall impairment of proliferation. The cell dynamic parameters differ from those measured in sheep, an experimental model for BLV infection. Finally, cells expressing p24 major capsid protein ex vivo were not BrdU positive, suggesting an immune selection against proliferating virus-positive lymphocytes. Based on a comparative leukemia approach, these observations might help to understand cell dynamics during other lymphoproliferative disease such as chronic lymphocytic leukemia or human T-cell lymphotropic virus-induced adult T-cell leukemia in humans.

Debacq, Christophe; Asquith, Becca; Reichert, Michal; Burny, Arsene; Kettmann, Richard; Willems, Luc

2003-01-01

373

Prevention of MDR Development in Leukemia Cells by Micelle-Forming Polymeric Surfactant  

PubMed Central

Doxorubicin (Dox) incorporated in nanosized polymeric micelles, SP1049C, has shown promise as monotherapy in patients with advanced esophageal carcinoma. The formulation contains amphiphilic block copolymers, Pluronics, that exhibit unique ability to chemosensitize multidrug resistant (MDR) tumors by inhibiting P-glycoprotein (Pgp) drug efflux system and enhancing pro-apoptotic signaling in cancer cells. This work evaluates whether a representative block copolymer, Pluronic P85 (P85) can also prevent development of Dox-induced MDR in leukemia cells. For in vitro studies murine lymphocytic leukemia cells (P388) were exposed to increasing concentrations of Dox with/without P85. For in vivo studies, BDF1 mice bearing P388 ascite were treated with Dox or Dox/P85. The selected P388 cell sublines and ascitic tumor-derived cells were characterized for Pgp expression and functional activity (RT-PCR, Western Blot, rhodamine 123 accumulation) as well as Dox resistance (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay). The global gene expression was determined by oligonucleotide gene microarrays. We demonstrated that P85 prevented development of MDR1 phenotype in leukemia cells in vitro and in vivo as determined by Pgp expression and functional assays of the selected cells. Cells selected with Dox in the presence of P85 in vitro and in vivo exhibited some increases in IC50 values compared to parental cells, but these values were much less than IC50 in respective cells selected with the drug alone. In addition to mdr1, P85 abolished alterations of genes implicated in apoptosis, drug metabolism, stress response, molecular transport and tumorigenesis. In conclusion, Pluronic formulation can prevent development of MDR in leukemia cells in vitro and in vivo.

Sharma, Amit K; Zhang, Li; Li, Shu; Kelly, David L.; Alakhov, Valery Yu.; Batrakova, Elena V.; Kabanov, Alexander V.

2009-01-01

374

The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells  

PubMed Central

A therapeutic strategy for treating cancer is to target and eradicate cancer stem cells (CSCs) without harming their normal stem cell counterparts. The success of this approach relies on identification of molecular pathways that selectively regulate CSC function. Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for CSCs, we show that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene through c-Myc in leukemia stem cells (LSCs) in CML mice and that Blk functions as a tumor suppressor in LSCs but does not affect normal hematopoietic stem cells (HSCs) or hematopoiesis. Blk suppresses LSC function through a pathway involving an upstream regulator, Pax5, and a downstream effector, p27. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. Blk also suppresses human CML stem cells. Our results demonstrate the feasibility of selectively targeting LSCs, an approach that should be applicable to other cancers.

Zhang, Haojian; Peng, Cong; Hu, Yiguo; Li, Huawei; Sheng, Zhi; Chen, Yaoyu; Sullivan, Con; Cerny, Jan; Hutchinson, Lloyd; Higgins, Anne; Miron, Patricia; Zhang, Xueqing; Brehm, Michael; Li, Dongguang; Green, Michael R.; Li, Shaoguang

2012-01-01

375

Kinetic analysis of cloning patterns by human marrow cells in leukemia.  

PubMed

In leukemia and preleukemic disorders the progeny of a single cell proliferate and ultimately come to occupy the hemopoietic system. In the process normal stem cells are suppressed and in time may become extinct. This implies that neoplastic clones have a biological advantage. In this paper evidence is presented that the cloning of granulocytic colony forming cells in the clonal hemopathies is influenced by cell products that regulate cloning of normal colony forming cells. We have attempted to develop an approach to the study of clone-clone interactions in order to determine at what level(s) the battle between clones is fought. Future studies on relative responsiveness might help in understanding the mechanisms by which normal hemopoiesis is suppressed during the evolution of leukemia and re-established during remission induction. PMID:3862490

Galbraith, P R; Cooke, L J; Galbraith, M A

1985-01-01

376

[The human T-cell leukemia virus type I (HTLV-I) tax protein induces apoptosis].  

PubMed

Human T-cell leukemia virus type I (HTLV-I) is an etiological agent of adult T-cell leukemia. The Tax protein of HTLV-I may play a central role in cellular transformation. By serum deprivation, Tax-transformed Rat-1 cells undergo apoptotic cell death. These cells exhibit DNA fragmentation and chromatin condensation. Constitutive expression of bcl-2, blocked Tax-mediated apoptosis. Activation of fusion protein containing Tax and estrogen receptor, also led to the trans-activation and caused inhibition of proliferation and apoptosis. However Tax inhibited anti-Apo-1-induced apoptosis. Apoptosis appear to be the most important process of HTLV-I associated myelopathy (HAM). In spinal cords from autopsied patients with HAM/TSP, apoptosis of helper-inducer T lymphocytes was observed. HTLV-I carrier WKAH rats developed myeloneuropathy and apoptotic death of oligodendrocytes. The apoptosis was consistent with HTLV-I pX expression. PMID:8741678

Yamada, T

1996-07-01

377

Leukemic cells growth fraction in the central nervous system in blastic phase of chronic myelogenous leukemia.  

PubMed

Clinical and neuropathological investigations were carried out in 6 patients, deceased due to blastic phase of chronic myelogenous leukemia (BPCML). Growth fraction of leukemic cells in peripheral blood, cerebrospinal fluid and in the central nervous system (CNS) was studied, using mitotic index and immunohistochemical staining technique with the monoclonal antibody antiproliferating cell nuclear antigen (anti-PCNA). The results suggest that in BPCML the proliferative activity of leukemic cells is low both in peripheral blood, cerebrospinal fluid, cerebral leukostasis and within the leptomeningeal and intracerebral infiltrates, even in cases with a very high white blood cells count. It can confirm the opinion that in BPCML, accumulation rather than proliferation of leukemic cells plays an important role in the development of the CNS leukemia. PMID:8629442

Zdziarska, B; Nowacki, P

1996-01-01

378

Evidence of B cell immune responses to acute lymphoblastic leukemia in murine allogeneic hematopoietic stem cell transplantation recipients treated with donor lymphocyte infusion and/or vaccination  

PubMed Central

These experiments explored mechanisms of control of acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation using a murine model of MHC-matched, minor histocompatibility antigen mismatched transplantation. The central hypothesis examined was that addition of active vaccination against leukemia cells would substantially increase the effectiveness of allogeneic donor lymphocyte infusion against ALL present in the host after transplant. While vaccination did increase the magnitude of type I T cell responses against leukemia cells associated with donor lymphocyte infusion, it did not lead to substantial improvement in long term survival. Analysis of immunological mechanisms of leukemia progression demonstrated that the failure of vaccination was not due to antigen loss in leukemia cells. However, analysis of survival provided surprising findings that, in addition to very modest type I T cell responses, a B cell response that produced antibodies that bind leukemia cells was found in long term survivors. The risk of death from leukemia was significantly lower in recipients that had higher levels of such antibodies. These studies raise the hypothesis that stimulation of B cell responses after transplant may provide a novel way to enhance allogeneic graft versus leukemia effects associated with transplantation.

Mullen, Craig A.; Campbell, Andrew; Tkachenko, Olena; Jansson, Johan; Hsu, Yu-chiao

2010-01-01

379

Adult T-cell leukemia/lymphoma in Jamaica and its relationship to human T-cell leukemia/lymphoma virus type I-associated lymphoproliferative disease.  

PubMed

We had shown previously that the prevalence of human T-cell leukemia/lymphoma virus type I (HTLV-I)-antibody positivity is high in Jamaican non-Hodgkin's lymphoma (NHL) patients and that virus-positive patients have the clinical features and poor prognosis of adult T-cell leukemia/lymphoma (ATL). Sixty-two % of 45 NHL patients diagnosed consecutively between 2/1/82 and 1/31/84 and studied prospectively were HTLV-I-antibody positive. Skin involvement (38%), hypercalcemia (44%), and leukemia (40%) were unusually prevalent and there was a strong association (p less than 0.05) with HTLV-I-antibody positivity. Fifty-two % of the patients had bone marrow infiltration, and 74% of these patients were HTLV-I-antibody positive (p = 0.06). Lymphadenopathy (96%), hepatomegaly (60%), and splenomegaly (25%) were detected with about the same frequency as in other series of NHL patients with advanced disease, and 61-88% of these patients were HTLV-I-antibody positive. Patients were classified into those with "typical ATL" (NHL associated with 2 of the 4 features i) hypercalcemia; ii) histologically proven skin infiltration; iii) leukemia; and iv) bone marrow infiltration, providing that the morphology of infiltrating or leukemic cells was characteristic of ATL; those "consistent with ATL" (NHL associated with 1 of these 4 features); and "non-ATL" (NHL without any of these 4 additional features). Thirty-two (71%) of the NHL patients were ATL patients, i.e., had features typical of or consistent with ATL, and 78% of these were HTLV-I-antibody positive. HTLV-I provirus was detected in tumour cells of all HTLV-I-antibody positive patients tested. Three (23%) of the non-ATL patients were HTLV-I-antibody positive. There was no correlation between histopathological features and the clinical classification or HTLV-I-antibody positivity. Median survival of ATL and non-ATL patients was 16 and 53 weeks. Although the disease was usually fulminant, 34% of the ATL patients had a subacute or chronic course. Skin involvement and leukemia were prominent in these patients. Hypercalcemia was the chief prognostic determinant. Median survival of hypercalcemic and normocalcemic ATL patients was 13 and 86 weeks (p less than 0.05). Hypercalcemia caused 10 deaths, infections 12, and death was due to tumour progression in 4 patients. Infections were usually due to pyogenic organisms and only 2 patients had systemic opportunistic infections. Six (27%) of 22 chronic lymphocytic leukemic (CLL) patients were HTLV-I-antibody positive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6100652

Gibbs, W N; Lofters, W S; Campbell, M; Hanchard, B; LaGrenade, L; Clark, J; Cranston, B; Saxinger, C; Gallo, R; Blattner, W A

1984-01-01

380

Hairy Root and Its Application in Plant Genetic Engineering  

Microsoft Academic Search

Agrobacterium rhizogenes Conn. causes hairy root disease in plants. Hairy root-infected A. rhizogenes is char- acterized by a high growth rate and genetic stability. Hairy root cultures have been proven to be an efficient means of producing secondary metabolites that are normally biosynthesized in roots of differentiated plants. Furthermore, a transgenic root system offers tremendous potential for introducing additional genes

Zhi-Bi Hu

381

Alkaloid production by hairy root cultures in Atropa belladonna  

Microsoft Academic Search

Hairy roots were induced by inoculation of stems of sterile plants of Atropa belladonna with Agrobacterium rhizogenes. The axenic culture of the hairy roots isolated from the stems proliferated 60 fold as based on the initial fresh weight after one month of culture. The presence of atropine and scopolamine in hairy roots were examined by TLC and HPLC. Their amounts

Hiroshi Kamada; Nobuyuki Okamura; Motoyoshi Satake; Hiroshi Harada; Koichiro Shimomura

1986-01-01

382

Transport of camptothecin in hairy roots of Ophiorrhiza pumila  

Microsoft Academic Search

We have investigated the subcellular accumulation and transport of camptothecin (CPT), a monoterpene indole alkaloid, in hairy roots of Ophiorrhiza pumila. This hairy root produces high amounts of CPT and excretes it into the culture medium. When the hairy roots were exposed to UV radiation, autofluorescence emitted from CPT showed subcellular localization of CPT in the vacuole. Treatment with several

Supaart Sirikantaramas; Hiroshi Sudo; Takashi Asano; Mami Yamazaki; Kazuki Saito

2007-01-01

383

Stem cell transplantation in pediatric leukemia and myelodysplasia: state of the art and current challenges.  

PubMed

The role of stem cell transplantation in the treatment of leukemia and myelodysplasia (MDS) in children has changed over the past decade. In pediatric acute lymphoblastic leukemia (ALL), the overall cure-rate is high with conventional chemotherapy. However, selected patients with a high-risk of relapse are often treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission (CR1). Patients with a bone-marrow relapse who attain a second remission frequently receive HSCT. High minimal residual disease (MRD) levels directly prior to HSCT determines the relapse risk. Therefore, MRD positive patients are eligible for more experimental approaches such as intensified or experimental chemotherapy pre-HSCT, as well as immune modulation post-HSCT. In pediatric acute myeloid leukemia (AML) the role of allo-HSCT in CR1 is declining, due to better outcome with modern multi-agent chemotherapy. In relapsed AML patients, allo-HSCT still seems indispensable. Targeted therapy may change the role of HSCT, in particular in chronic myeloid leukemia, where the role of allografting is changing in the imatinib era. In MDS, patients are usually transplanted immediately without prior cytoreduction. New developments in HSCT, such as the role of alternative conditioning regimens, and innovative stem cell sources such as peripheral blood and cord blood, will also be addressed. PMID:18240454

Bierings, Marc; Nachman, James B; Zwaan, C Michel

2007-01-01

384

Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells.  

PubMed

Mitochondrial damage with release of cytochrome c is implicated in cell death signalling pathways. To examine mitochondrial function in apoptotic cells, we applied high-resolution respirometry to human leukemia cells arrested in the G1- and S-phase by exposure to the glucocorticoid dexamethasone and nucleotide analogue gemcitabine. At 30% apoptosis, opposite effects were observed on respiratory capacity (71% and 131% of controls, respectively). These changes correlated with alterations in cell size, cytosolic, and mitochondrial marker enzymes. Mitochondrial ATP production and membrane potential were maintained in all treatments, as deduced from high respiratory uncoupling control ratios (UCR). Bcl-2 over-expression did not prevent apoptosis after gemcitabine-treatment, but protected dexamethasone-treated cells from apoptosis, without fully preventing the decline of respiration and cell size. These results, therefore, provide conclusive evidence that alterations in respiratory capacity and enzyme activities per cell are mainly caused by opposite changes in cell size, occurring upon cell cycle arrest triggered by dexamethasone and gemcitabine in the early phase of apoptosis. PMID:12972300

Renner, Kathrin; Amberger, Albert; Konwalinka, Günther; Kofler, Reinhard; Gnaiger, Erich

2003-09-23

385

Leukemogenicity andCellTransformation Mechanisms In Vitro byGross MurineLeukemia Virus: Analysis ofVirus Subpopulations  

Microsoft Academic Search

Theleukemogenic activity ofGrossmurine leukemia virus adapted toratswas tested inW\\/FuratsandNIH\\/Swiss mice.Allanimals infected withthisvirus developed thymic andnonthymic T-cell leukemia witha short latency period. It was observed thatcell-free extracts fromthymiclymphomatissue ofmiceand rats, induced byeither Grossmurineleukemia virus or Grossmurine leukemia virus adapted torats, consisted ofbothsmall-plaque-forming andlarge-plaque- forming viruses, asdetermined bytheXC plaque test. MCF-typevirus was found inthese virus complexes. Transformed cell foci were induced inSC-1cell

KATSUTOMO HAMADA; KAZUYOSHI YANAGIHARA; KENJI KAMIYA; TOSHIO SEYAMA; KENJIRO YOKORO

1981-01-01

386

Adenosine deaminase (ADA) in leukemia: clinical value of plasma ADA activity and characterization of leukemic cell ADA.  

PubMed

Adenosine deaminase (ADA) activity was measured in plasma, erythrocytes, and mononuclear cells from 18 patients with acute and chronic leukemia. High levels of ADA activities were found in plasma, erythrocytes, and mononuclear cells from patients with acute leukemia, especially acute lymphoblastic leukemia, and blastic crisis of chronic myeloid leukemia. Serial determination of plasma ADA activities was done in 9 patients with acute leukemia. All patients untreated or in relapse had an elevation of plasma ADA activity, which decreased to normal or subnormal levels during complete remission. On starch gel electrophoresis, plasma ADA in leukemic patients separated into two bands. The major band showed a mobility identical to that of normal red cells and mononuclear cells, and the minor band corresponded to that of normal plasma ADA. Enzymatic and immunological studies were performed on ADA from leukemic cells of acute myeloid and lymphoblastic leukemia. There were no differences in Michaelis constant for adenosine, thermostability, electrophoretic mobility, immunological reactivity, and specific activity between ADA of leukemic cells and normal mononuclear cells. These results strongly suggest that the increased ADA activity in leukemic cells is caused by an increased synthesis of a structurally normal enzyme and that increased plasma ADA activity in leukemic patients reflects an increment of leukemic cells in bone marrow. Therefore, serial determination of plasma ADA activities seems to provide a good indicator of the total mass of leukemic cells in bone marrow. PMID:3985005

Morisaki, T; Fujii, H; Miwa, S

1985-05-01

387

Sorafenib-Induced Apoptosis of Chronic Lymphocytic Leukemia Cells Is Associated with Downregulation of RAF and Myeloid Cell Leukemia Sequence 1 (Mcl-1)  

PubMed Central

We have previously shown that sorafenib, a multikinase inhibitor, exhibits cytotoxic effects on chronic lymphocytic leukemia (CLL) cells. Because the cellular microenvironment can protect CLL cells from drug-induced apoptosis, it is important to evaluate the effect of novel drugs in this context. Here we characterized the in vitro cytotoxic effects of sorafenib on CLL cells and the underlying mechanism in the presence of marrow stromal cells (MSCs) and nurselike cells (NLCs). One single dose of 10 ?mol/L or the repeated addition of 1 ?mol/L sorafenib caused caspase-dependent apoptosis and reduced levels of phosphorylated B-RAF, C-RAF, extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia sequence 1 (Mcl-1) in CLL cells in the presence of the microenvironment. We show that the RAF/mitogen-activated protein kinase kinase (MEK)/ERK pathway can modulate Mcl-1 expression and contribute to CLL cell viability, thereby associating so-rafenib cytotoxicity to its impact on RAF and Mcl-1. To evaluate if the other targets of sorafenib can affect CLL cell viability and contribute to sorafenib-mediated cytotoxicity, we tested the sensitivity of CLL cells to several kinase inhibitors specific for these targets. Our data show that RAF and vascular endothelial growth factor receptor (VEGFR) but not KIT, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) are critical for CLL cell viability. Taken together, our data suggest that sorafenib exerts its cytotoxic effect likely via inhibition of the VEGFR and RAF/MEK/ERK pathways, both of which can modulate Mcl-1 expression in CLL cells. Furthermore, sorafenib induced apoptosis of CLL cells from fludarabine refractory patients in the presence of NLCs or MSCs. Our results warrant further clinical exploration of sorafenib in CLL.

Fecteau, Jessie-F; Bharati, Ila S; O'Hayre, Morgan; Handel, Tracy M; Kipps, Thomas J; Messmer, Davorka

2012-01-01

388

G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus  

PubMed Central

A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia- incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.

1978-01-01

389

Resveratrol inhibits the secretion of vascular endothelial growth factor and subsequent proliferation in human leukemia U937 cells  

Microsoft Academic Search

Summary  This study examined the effect of resveratrol on the secretion of vascular endothelial growth factor (VEGF) and subsequent\\u000a proliferation of human leukemia U937 cells, and explored the mechanisms involved. Human leukemia U937 cells were treated with\\u000a resveratrol of different concentrations (12.5–200 ?mol\\/L) for different time lengths (12–48 h). The proliferation of the U937\\u000a leukemic cells was determined by MTT assay.

Zehai Tang; Xin-yue Liu; Ping Zou

2007-01-01

390

HTLV-V: A New Human Retrovirus Isolated in a Tac-Negative T Cell Lymphoma\\/Leukemia  

Microsoft Academic Search

A new human retrovirus was isolated from a continuous cell line derived from a patient with CD4+ Tac- cutaneous T cell lymphoma\\/leukemia. This virus is related to but distinct from human T cell leukemia\\/lymphoma virus types I and II (HTLV-I and HTLV-II) and human immunodeficiency virus (HIV-1). With the use of a fragment of provirus cloned from one patient with

Vittorio Manzari; Angela Gismondi; Giovanni Barillari; Stefania Morrone; Andrea Modesti; Loredana Albonici; Laura de Marchis; Vito Fazio; Angela Gradilone; Massimo Zani; Luigi Frati; Angela Santoni

1987-01-01

391

Differential expression of the ufo/axl oncogene in human leukemia-lymphoma cell lines.  

PubMed

The ufo protein (also termed axl) is a member of a new family of receptor tyrosine kinases and is encoded by a transforming gene that was initially isolated from primary human myeloid leukemia cells by DNA-mediated transformation of NIH/3T3 cells. The ligand, Gas6, a protein S-related molecule lacking any known function yet, has recently been identified. We report the expression pattern of ufo mRNA in a panel of 76 human continuous leukemia-lymphoma cell lines. The gene was not expressed in cell lines derived from lymphoid malignancies (n=28), but transcription was seen in 3/11 myeloid, 0/6 monocytic, 9/13 erythroid and 11/18 megakaryocytic cell lines. Several cell lines were treated with phorbol ester leading to significant upregulation of the ufo message in constitutively positive cells. An apparent ufo mRNA overexpression was not found in any of the positive leukemia cell lines, but was identified in the drug-resistant subclones of the cervix carcinoma cell line HeLa. Southern blot analysis of restriction enzyme-digested genomic DNA did not provide evidence for gene amplification, but the HeLa subclones showed banding patterns suggestive of gene rearrangement. Two main ufo mRNA bands of 3.2 and 5.0 kb were identified; no differences in the half-lives (t1/2 = 2.5 h) of these two mRNA species could be identified. In summary, ufo, representing a novel type of receptor tyrosine kinase, is expressed solely in myeloid and erythro-megakaryocytic leukemias but not in lymphoid malignancies. These and previous data suggest an involvement of the ufo receptor tyrosine kinase in normal and malignant myelopoiesis; however, its exact role, if any, and mode of operation in leukemogenesis remains to be determined. PMID:8656672

Challier, C; Uphoff, C C; Janssen, J W; Drexler, H G

1996-05-01

392

The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+ T-cell line with potent in vivo graft-versus-leukemia properties.  

PubMed

Relapse is more frequent after autologous than allogeneic bone marrow transplantation (BMT), due in part to lack of T-lymphocyte mediated allogeneic graft-versus-leukemia (GVL) effects. Infusions of leukemia-reactive T cells to patients after autologous BMT may be a means for providing a GVL effect. Costimulation of T cells by binding of the CD28 receptor on T cells with B7-counter receptors on antigen presenting cells amplifies antigen-specific T-cell responses. To enhance generation of leukemia reactive cytotoxic T lymphocytes (CTL), the murine B7-1- and B7-2-costimulatory molecule cDNAs were introduced into the MHC class I+, class II-, murine meyloid leukemia cell line C1498. B7-1 expression greatly enhanced the ability of the leukemia cells to generate and expand leukemia reactive CTL in vitro. A highly cytolytic and C1498 specific CD8+ CTL line was generated by B7-1 costimulation. This CTL line proliferated autonomously and produced interleukin-2 when provided B7-1 or B7-2 costimulation by C1498 leukemia cells. To test the in vivo antileukemia properties of this CTL line, irradiated syngeneic BMT recipients were given graded doses of leukemia cells on day 0, followed by CTL infusions beginning on day 1 post-BMT. Recipients of 10(7) CTL had a 3 log reduction in leukemia burden such that 100% of mice were protected from a supralethal leukemic cell dose. Sustained immune responses were detectable up to 3 months postinfusion of the CTL line. B7-1 or B7-2 costimulation in vivo did not augment antileukemia effects of infused CTL post BMT. These results suggest that B7 costimulation of leukemia reactive CTL may be important for their ex vivo generation and expansion for use in human adoptive immunotherapy of leukemia. PMID:9129056

Boyer, M W; Vallera, D A; Taylor, P A; Gray, G S; Katsanis, E; Gorden, K; Orchard, P J; Blazar, B R

1997-05-01

393

The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia  

PubMed Central

Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to ?-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to ?-secretase inhibitors.

Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

2012-01-01

394

Triptolide induced cytotoxic effects on human promyelocytic leukemia, T cell lymphoma and human hepatocellular carcinoma cell lines  

Microsoft Academic Search

Triptolide, a traditional Chinese medicine, has been reported to be effective in the treatment of auto-immune diseases, and it can also induce anti-neoplastic activity on several human tumor cell lines. This study investigates the cytotoxic function and the functional mechanism of triptolide on tumor cells. Promyelocytic leukemia, (HL-60), T cell lymphoma (Jurkat), and human hepatocelluar carcinoma (SMMC-7721) cells were subjected

Ella Wai-Ching Chan; Samuel Chak-Sum Cheng; Fion Wan-Yee Sin; Yong Xie

2001-01-01

395

Further Electron Microscope Studies of a Mouse Leukemia Induced by Cell-Free Filtrates  

PubMed Central

Further electron microscope observations of tissues from Swiss and DBA/2 mice with leukemia transmissible by cell-free filtrates to the adult animals are presented. The cytological characteristics of the leukemic cells, the fine structure of the viruses, and the virus host-cell relationships have been examined. The leukemia virus has an external diameter averaging 870 A, and appears to be formed at the level of cell membranes by a budding process. The viruses are observed most frequently in intercellular spaces, but are also often found within cytoplasmic vacuoles of megakaryocytes. Lead hydroxide staining was applied to the study of the leukemic material. The viruses have been found to have a considerable affinity for this lead salt, only comparable in intensity to the affinity shown by RNP granules for the same chemical.

de Harven, Etienne; Friend, Charlotte

1960-01-01

396

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.  

PubMed

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs. PMID:19182207

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G

2009-01-30

397

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras  

PubMed Central

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Langer, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R.

2009-01-01

398

TRIM5 mediates the postentry block to N-tropic murine leukemia viruses in human cells  

Microsoft Academic Search

Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon after virus entry into the cell

Michel J. Perron; Matthew Stremlau; Byeongwoon Song; Wes Ulm; Richard C. Mulligan; Joseph Sodroski

2004-01-01

399

Binding Kinetics of Ecotropic (Moloney) Murine Leukemia Retrovirus with NIH 3T3 Cells  

Microsoft Academic Search

A quantitative analysis of the binding kinetics of intact Moloney murine leukemia retrovirus (MoMuLV) particles with NIH 3T3 cells was performed with an immunofluorescenceflow cytometry assay. The virus-cell binding equilibrium dissociation constant (KD), expressed in terms of virus particle concentration, was measured to be 8.5 (66.4) 310 212 Mat4 &C and was three- to sixfold lower at temperatures above 15&C.

HONG YU; FRENCH ANDERSON

1995-01-01

400

Cupric nitrilotriacetate induces oxidative DNA damage and apoptosis in human leukemia HL60 cells  

Microsoft Academic Search

Recent reports have implicated a possible role of reactive oxygen species (ROS) in the induction and mediation of apoptosis and DNA damage. Oxidative DNA base modification induced by cupric nitrilotriacetate (Cu-NTA) and the following apoptosis were observed in human promyelocytic leukemia HL-60 cells. We measured the level of ROS in the cells by using a fluorescence probe, 2?,7?-dichlorofluorescein diacetate (DCFH-DA),

Yuxiang Ma; Liu Cao; Teruyuki Kawabata; Tadashi Yoshino; Burton B. Yang; Shigeru Okada

1998-01-01

401

Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia  

Microsoft Academic Search

The role of chimerism analysis as a prognostic indicator of relapse after hematopoietic stem cell transplantation (SCT) is controversial. We monitored chimerism status by short tandem repeat-based polymerase chain reaction (PCR) in T- and non-T-cell subsets and retrospectively evaluated clinical outcome in 96 patients with acute myeloid leukemia after myeloablative (MA) or reduced-intensity conditioning SCT. Fifty-six percent of 80 patients

C Huisman; R A de Weger; L de Vries; M G J Tilanus; L F Verdonck

2007-01-01

402

Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL60 cells  

Microsoft Academic Search

Pycnogenol, rich of many phytochemicals of medical value, is a commercialized nutrient supplement extracted from the bark of European coastal pine. In this study, we investigated the anti-tumor effects of Pycnogenol on HL-60, U937 and K562 human leukemia cell lines. We found that Pycnogenol inhibited cell proliferation dose- and time-dependently, and the IC50s of Pycnogenol on HL-60, U937 and K562

W. W. Huang; J. S. Yang; C. F. Lin; W. J. Ho; M. R. Lee

2005-01-01

403

Expression of Cellular Oncogenes in Primary Cells from Human Acute Leukemias  

Microsoft Academic Search

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was

F. Mavilio; N. M. Sposi; M. Petrini; L. Bottero; M. Marinucci; G. de Rossi; S. Amadori; F. Mandelli; C. Peschle

1986-01-01

404

Disseminated Strongyloides stercoralis Infection in HTLV1Associated Adult T-Cell Leukemia\\/Lymphoma  

Microsoft Academic Search

A 55-year-old woman with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL) and a history of previously treated Strongyloides stercoralis infection received anti-CD52 monoclonal antibody therapy with alemtuzumab on a clinical trial. After an initial response, she developed ocular involvement by ATL. Alemtuzumab was stopped and high-dose corticosteroid therapy was started to palliate her ocular symptoms. Ten days

Donn M. Stewart; Roshan Ramanathan; Siddhartha Mahanty; Daniel P. Fedorko; John E. Janik; John C. Morris

2011-01-01

405

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

Microsoft Academic Search

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

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

406

Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells  

Microsoft Academic Search

Curcumin, widely used as a spice and coloring agent in food, possesses potent antioxidant, anti-inflammatory and anti-tumor promoting activities. In the present study, curcumin was found to induce apoptotic cell death in promyelocytic leukemia HL-60 cells at concentrations as low as 3.5 ?g\\/ml. The apoptosis-inducing activity of curcumin appeared in a dose- and time-dependent manner. Flow cytometric analysis showed that

Min-Liang Kuo; Tze-Sing Huang

1996-01-01

407

Electron microscopy localization and characterization of functionalized composite organic-inorganic SERS nanoparticles on leukemia cells  

Microsoft Academic Search

We demonstrate the use of electron microscopy as a powerful characterization tool to identify and locate antibody-conjugated composite organic-inorganic nanoparticle (COINs) surface enhanced Raman scattering (SERS) nanoparticles on cells. U937 leukemia cells labeled with antibody CD54-conjugated COINs were characterized in their native, hydrated state using wet scanning electron microscopy (SEM) and in their dehydrated state using high-resolution SEM. In both

Ai Leen Koh; Catherine M. Shachaf; Sailaja Elchuri; Garry P. Nolan; Robert Sinclair

2008-01-01

408

Apparent expansion of CD34+ cells during the evolution of myelodysplastic syndromes to acute myeloid leukemia  

Microsoft Academic Search

Myelodysplastic syndromes (MDS) are highly proliferative bone marrow (BM) disorders where the primary lesion presumably affects a CD34+ early progenitor or stem cell. We investigated the proliferative characteristics of CD34+ cells of 33 untreated MDS patients (19 RA, 5 RARS, 7 RAEB, 2 RAEBt) and five patients with acute myeloid leukemia after MDS (sAML). All patients received a 1-h infusion

LFR Span; SE Dar; V Shetty; SD Mundle; L Broady-Robinson; S Alvi; RAP Raymakers; T de Witte; A Raza

1998-01-01

409

Treatment of relapsing leukemia after allogeneic blood stem cell transplantation by using dose-reduced conditioning followed by donor blood stem cells and GM-CSF  

Microsoft Academic Search

Ten patients with high-risk acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) relapsing early ( n=8) or late (̿ year, n=2) after allogeneic transplantation were treated with cytoreductive chemotherapy followed by unmanipulated peripheral blood stem cell transplantation (PBSCT) from related (n=3) and unrelated donors (n=7). In order to enhance the graft-versus-leukemia effect, patients received no graft-versus-host

Uwe Platzbecker; Christian Thiede; Jens Freiberg-Richter; Anett Helwig; Brigitte Mohr; Gabriele Prange; Monika Füssel; Thomas Köhler; Gerhard Ehninger; Martin Bornhäuser

2001-01-01

410

Identification of an FMR cell surface antigen associated with murine leukemia virus-infected cells.  

PubMed Central

FMR antigens are found on the surface of cells infected with Friend, Moloney, and Rauscher murine leukemia viruses (MuLV). These antigens are serologically distinct from the G cell surface antigens that are found on cells infected with endogenous MuLV (AKR and Gross virus). Cell surface antigens of both virus groups are immunogenic in mice, and immunization with appropriate virus-infected cells leads to the production of cytotoxic antisera. The cytotoxic activity of FMR antisera can be absorbed by disrupted preparations of Rauscher MuLV, but not by AKR MuLV. FMR antisera precipitate the viral envelope proteins gp70, pl5(E), and p12(E) from detergent-disrupted preparations of [3H]leucine-labeled MuLV. The reaction of these antisera with p15(E) and p12(E) proteins is directed against group-specific antigens and can be absorbed with AKR MuLV; in contrast, the reaction of these antisera with gp70 is directed against type-specific antigens and is absorbed only by viruses of the FMR group. In immune precipitation assays with detergent-disrupted 125I surface-labeled cells, FMR antisera react only with type-specific antigens of the viral envelpe protein. On the basis of these findings we conclude that the FMR cell surface antigen is a determinant on the MuLV env gene product. Images

Nowinski, R C; Emery, S; Ledbetter, J

1978-01-01

411

Detection of mRNA for the tax sub 1 \\/rex sub 1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction  

Microsoft Academic Search

Expression of human T-cell leukemia virus type I (HTLV-I) is not detectable by immunofluorescence analysis or RNA blot analysis in most fresh peripheral blood mononuclear cells of patients with adult T-cell leukemia or of asymptomatic HTLV-I carriers. However, in this work, mRNA for the HTLV-I taxâ\\/rex⁠genes was detected in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients

Tomohiro Kinoshita; Masanori Shimoyama; Kensei Tobinai; Mizuko Ito; Shinichiro Ito; Shuichi Ikeda; Kazuo Tajima; Kunitada Shimotohno; Takashi Shugimura

1989-01-01

412

Implication of Early Lymphocyte Recovery after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Leukemia  

PubMed Central

Purpose The repopulating lymphocytes after allogeneic hematopoietic stem cell transplantation have an important role not only on the prevention of serious infections in the early transplantation period, but also on the killing of residual leukemic cells by graft-versus-leukemia effect. The aim of this study was to analyze the impact of lymphocyte recovery after allogeneic stem cell transplantation in children with hematologic malignancies. Materials and Methods We evaluated 69 children transplanted for acute lymphoblastic leukemia (ALL) (n=34), acute myeloid leukemia (AML) (n=26), chronic leukemia (n=7) and juvenile myelomonocytic leukemia (n=2) between 1996 and 2008 at the Chonnam National University Hospital, Korea. The patients were grouped based on absolute lymphocyte counts (ALC) <500/µL or ?500/µL at D+21 and D+30 after transplant. Results Patients with a High ALC at D+21 and D+30 had a faster neutrophil and platelet engraftment. The High at D+30 group had a better 5 year overall survival (71% vs. 53%, p=0.043) and event-free survival (72% vs. 53%, p=0.065) than the Low at D+30 group. The incidence of grade II-IV acute and chronic graft-versus-host disease (GVHD), and relapse rate did not differ by the ALC counts. However, the Low at D+30 group had a significantly increased risk for transplant-related mortality (p=0.019). The univariate analysis showed that the factors associated with decreased survival were a Low ALC at D+30, patients with high risk ALL, and grade II-IV aGVHD in patients with ALL and AML. Conclusion Early posttransplant serial lymphocyte measurement would be a simple but useful method for predicting transplant outcomes.

Han, Dong Kyun; Baek, Hee Jo; Kim, So Yeon; Hwang, Tai Ju

2013-01-01

413

Leukemia cell to endothelial cell communication via exosomal miRNAs.  

PubMed

Recent findings indicate that specific microRNAs (miRNAs), such as those of the miR-17-92 cluster, may be responsible for regulating endothelial gene expression during tumor angiogenesis. Secreted miRNAs enclosed in exosomes also have an important role in cell-cell communication. To elucidate whether miRNAs secreted from neoplastic cells transfer into endothelial cells and are functionally active in the recipient cells, we investigated the effect of exosomal miRNAs derived from leukemia cells (K562) on human umbilical vein endothelial cells (HUVECs). As K562 cells released the miR-17-92 cluster, especially miR-92a, into the extracellular environment, K562 cells, transfected with Cy3-labeled pre-miR-92a, were co-cultured with HUVECs. Cy3-miR-92a derived from K562 cells was detected in the cytoplasm of HUVECs, and the Cy3-miR-92a co-localized with the signals of an exosomal marker, CD63. The expression of integrin ?5, a target gene for miR-92a, was significantly reduced in HUVECs by exosomal miR-92a, indicating that exogenous miRNA via exosomal transport can function like endogenous miRNA in HUVECs. The most salient feature of this study is the exosome, derived from K562 cells with enforced miR-92a expression, did not affect the growth of HUVECs but did enhance endothelial cell migration and tube formation. Our results support the idea that exosomal miRNAs have an important role in neoplasia-to-endothelial cell communication. PMID:22797057

Umezu, T; Ohyashiki, K; Kuroda, M; Ohyashiki, J H

2012-07-16

414

Disruption of SIRP? signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts.  

PubMed

Although tumor surveillance by T and B lymphocytes is well studied, the role of innate immune cells, in particular macrophages, is less clear. Moreover, the existence of subclonal genetic and functional diversity in some human cancers such as leukemia underscores the importance of defining tumor surveillance mechanisms that effectively target the disease-sustaining cancer stem cells in addition to bulk cells. In this study, we report that leukemia stem cell function in xenotransplant models of acute myeloid leukemia (AML) depends on SIRP?-mediated inhibition of macrophages through engagement with its ligand CD47. We generated mice expressing SIRP? variants with differential ability to bind human CD47 and demonstrated that macrophage-mediated phagocytosis and clearance of AML stem cells depend on absent SIRP? signaling. We obtained independent confirmation of the genetic restriction observed in our mouse models by using SIRP?-Fc fusion protein to disrupt SIRP?-CD47 engagement. Treatment with SIRP?-Fc enhanced phagocytosis of AML cells by both mouse and human macrophages and impaired leukemic engraftment in mice. Importantly, SIRP?-Fc treatment did not significantly enhance phagocytosis of normal hematopoietic targets. These findings support the development of therapeutics that antagonize SIRP? signaling to enhance macrophage-mediated elimination of AML. PMID:22945919

Theocharides, Alexandre P A; Jin, Liqing; Cheng, Po-Yan; Prasolava, Tatiana K; Malko, Andrei V; Ho, Jenny M; Poeppl, Armando G; van Rooijen, Nico; Minden, Mark D; Danska, Jayne S; Dick, John E; Wang, Jean C Y

2012-09-03

415

Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells  

PubMed Central

Post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 has been shown to improve leukemia-free survival in acute myeloid leukemia in a phase III trial. For this study, treatment efficacy was determined among 145 trial patients with morphological forms of acute myeloid leukemia as defined by the French-American-British classification. Leukemia-free survival was strongly improved in M4/M5 (myelomonocytic/monocytic) leukemia but not in M2 (myeloblastic) leukemia. We also analyzed histamine H2 receptor expression by leukemic cells recovered from 26 newly diagnosed patients. H2 receptors were typically absent from M2 cells but frequently expressed by M4/M5 cells. M4/M5 cells, but not M2 cells, produced reactive oxygen species that triggered apoptosis in adjacent natural killer cells. These events were significantly inhibited by histamine dihydrochloride. Our data demonstrate the presence of functional histamine H2 receptors on human AML cells and suggest that expression of these receptors by leukemic cells may impact on the effectiveness of histamine-based immunotherapy.

Aurelius, Johan; Martner, Anna; Brune, Mats; Palmqvist, Lars; Hansson, Markus; Hellstrand, Kristoffer; Thoren, Fredrik B.

2012-01-01

416

PCFT/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells  

SciTech Connect

The proton-coupled folate transporter (PCFT/SLC46A1) displays optimal and prominent folate and antifolate transport activity at acidic pH in human carcinoma cells but poor activity in leukemia cells. Consistently herein, human leukemia cell lines expressed poor PCFT transcript levels, whereas various carcinoma cell lines showed substantial PCFT gene expression. We identified a CpG island with high density at nucleotides -200 through +100 and explored its role in PCFT promoter silencing. Leukemia cells with barely detectable PCFT transcripts consistently harbored 85-100% methylation of this CpG island, whereas no methylation was found in carcinoma cells. Treatment with 5-Aza-2'-deoxycytidine which induced demethylation but not with the histone deacetylase inhibitor trichostatin A, restored 50-fold PCFT expression only in leukemia cells. These findings constitute the first demonstration of the dominant epigenetic silencing of the PCFT gene in leukemia cells. The potential translational implications of the restoration of PCFT expression in chemotherapy of leukemia are discussed.

Gonen, Nitzan; Bram, Eran E. [Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel); Assaraf, Yehuda G. [Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa 32000 (Israel)], E-mail: assaraf@tx.technion.ac.il

2008-11-28

417

Functional leukemia-associated antigen-specific memory CD8 T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation  

Microsoft Academic Search

Antigens implicated in the graft-versus- leukemia (GVL) effect in chronic my- eloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low fre- quencies of these antigen-specific CD8 T cells, we used quantitative polymer- ase chain reaction (qPCR) to measure interferon- (IFN-) mRNA production by peptide-pulsed CD8 T cells from HLA-A*0201 healthy volunteers and from patients with CML before

Katayoun Rezvani; Matthias Grube; Jason M. Brenchley; Giuseppe Sconocchia; Hiroshi Fujiwara; David A. Price; Emma Gostick; Ko Yamada; Jan Melenhorst; Richard Childs; Nancy Hensel; Daniel C. Douek; A. John Barrett; John Barrett

2003-01-01

418