Science.gov

Sample records for myeloid leukemia reveals

  1. What Is Acute Myeloid Leukemia?

    MedlinePlus

    ... about acute myeloid leukemia? What is acute myeloid leukemia? Cancer starts when cells in a part of ... the body from doing their jobs. Types of leukemia Not all leukemias are the same. There are ...

  2. What Is Chronic Myeloid Leukemia?

    MedlinePlus

    ... leukemia? Next Topic Normal bone marrow and blood What is chronic myeloid leukemia? Cancer starts when cells ... their treatment is the same as for adults. What is leukemia? Leukemia is a cancer that starts ...

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

    ClinicalTrials.gov

    2016-08-10

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  4. Myeloid leukemia after hematotoxins.

    PubMed Central

    Larson, R A; LeBeau, M M; Vardiman, J W; Rowley, J D

    1996-01-01

    One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogenic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase II, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11q23 or 21q22. The MLL gene at 11q23 or the AML1 gene at 21q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 11q23 rearrangements. Therapy-related leukemias with 11q23 or 21q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts. PMID:9118910

  5. Myeloid leukemia after hematotoxins

    SciTech Connect

    Larson, R.A.; LeBeau, M.M.; Vardiman, J.W.; Rowley, J.D.

    1996-12-01

    One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogeneic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase 11, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11 q23 or 21 q22. The MLL gene at 11 q23 or the AML1 gene at 21 q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 1 1 q23 rearrangements. Therapy-related leukemias with 11 q23 or 21 q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts. 32 refs., 4 tabs.

  6. Genome wide analysis of acute myeloid leukemia reveal leukemia specific methylome and subtype specific hypomethylation of repeats.

    PubMed

    Saied, Marwa H; Marzec, Jacek; Khalid, Sabah; Smith, Paul; Down, Thomas A; Rakyan, Vardhman K; Molloy, Gael; Raghavan, Manoj; Debernardi, Silvana; Young, Bryan D

    2012-01-01

    Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R(2) = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array. PMID:22479372

  7. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-05-18

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

  9. The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations.

    PubMed

    Bodini, Margherita; Ronchini, Chiara; Giacò, Luciano; Russo, Anna; Melloni, Giorgio E M; Luzi, Lucilla; Sardella, Domenico; Volorio, Sara; Hasan, Syed K; Ottone, Tiziana; Lavorgna, Serena; Lo-Coco, Francesco; Candoni, Anna; Fanin, Renato; Toffoletti, Eleonora; Iacobucci, Ilaria; Martinelli, Giovanni; Cignetti, Alessandro; Tarella, Corrado; Bernard, Loris; Pelicci, Pier Giuseppe; Riva, Laura

    2015-01-22

    The analyses carried out using 2 different bioinformatics pipelines (SomaticSniper and MuTect) on the same set of genomic data from 133 acute myeloid leukemia (AML) patients, sequenced inside the Cancer Genome Atlas project, gave discrepant results. We subsequently tested these 2 variant-calling pipelines on 20 leukemia samples from our series (19 primary AMLs and 1 secondary AML). By validating many of the predicted somatic variants (variant allele frequencies ranging from 100% to 5%), we observed significantly different calling efficiencies. In particular, despite relatively high specificity, sensitivity was poor in both pipelines resulting in a high rate of false negatives. Our findings raise the possibility that landscapes of AML genomes might be more complex than previously reported and characterized by the presence of hundreds of genes mutated at low variant allele frequency, suggesting that the application of genome sequencing to the clinic requires a careful and critical evaluation. We think that improvements in technology and workflow standardization, through the generation of clear experimental and bioinformatics guidelines, are fundamental to translate the use of next-generation sequencing from research to the clinic and to transform genomic information into better diagnosis and outcomes for the patient. PMID:25499761

  10. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  11. Stages of Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  12. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  13. General Information about Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-23

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

  15. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-11

    Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder

  16. Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-03-10

    Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Multilineage Dysplasia; Myeloid Sarcoma; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome

  17. Acute myeloid leukemia.

    PubMed

    Appelbaum, F R; Rowe, J M; Radich, J; Dick, J E

    2001-01-01

    Through the hard work of a large number of investigators, the biology of acute myeloid leukemia (AML) is becoming increasingly well understood, and as a consequence, new therapeutic targets have been identified and new model systems have been developed for testing novel therapies. How these new therapies can be most effectively studied in the clinic and whether they will ultimately improve cure rates are questions of enormous importance. In this article, Dr. Jacob Rowe presents a summary of the current state-of-the-art therapy for adult AML. His contribution emphasizes the fact that AML is not a single disease, but a number of related diseases each distinguished by unique cytogenetic markers which in turn help determine the most appropriate treatment. Dr. Jerald Radich continues on this theme, emphasizing how these cytogenetic abnormalities, as well as other mutations, give rise to abnormal signal transduction and how these abnormal pathways may represent ideal targets for the development of new therapeutics. A third contribution by Dr. Frederick Appelbaum describes how AML might be made the target of immunologic attack. Specifically, strategies using antibody-based or cell-based immunotherapies are described including the use of unmodified antibodies, drug conjugates, radioimmunoconjugates, non-ablative allogeneic transplantation, T cell adoptive immunotherapy and AML vaccines. Finally, Dr. John Dick provides a review of the development of the NOD/SCID mouse model of human AML emphasizing both what it has taught us about the biology of the disease as well as how it can be used to test new therapies. Taken together, these reviews are meant to help us understand more about where we are in the treatment of AML, where we can go and how we might get there. PMID:11722979

  18. Chronic Myeloid Leukemia

    MedlinePlus

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

  19. Acute Myeloid Leukemia

    MedlinePlus

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

  20. Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

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

  3. Genetics Home Reference: core binding factor acute myeloid leukemia

    MedlinePlus

    ... acute myeloid leukemia core binding factor acute myeloid leukemia Enable Javascript to view the expand/collapse boxes. ... Close All Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  4. What Are the Key Statistics about Acute Myeloid Leukemia?

    MedlinePlus

    ... for acute myeloid leukemia? What are the key statistics about acute myeloid leukemia? The American Cancer Society’s ... myeloid leukemia .” Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  5. Chronic Myeloid Leukemia

    MedlinePlus

    ... some patients with acute lymphoblastic leukemia (ALL). One theory that scientists propose about why this switch occurs ... a result called “graft-versus-tumor effect”). The theory being tested with a reduced-intensity transplant is ...

  6. Acute myeloid leukemia

    MedlinePlus

    ... a low number of platelets. A white blood cell count ( WBC ) can be high, low, or normal. Bone ... and overall health How high your white blood cell count was Certain genetic changes in the leukemia cells ...

  7. Endometrial and acute myeloid leukemia cancer genomes characterized

    Cancer.gov

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers with the potential to i

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

    ClinicalTrials.gov

    2015-07-27

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

  9. Clonal Evolution Revealed by Whole Genome Sequencing in a Case of Primary Myelofibrosis Transformed to Secondary Acute Myeloid Leukemia

    PubMed Central

    Engle, Elizabeth K.; Fisher, Daniel A.C.; Miller, Christopher A.; McLellan, Michael D.; Fulton, Robert S.; Moore, Deborah M.; Wilson, Richard K.; Ley, Timothy J.; Oh, Stephen T.

    2014-01-01

    Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML. PMID:25252869

  10. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

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

  11. Recognizing familial myeloid leukemia in adults

    PubMed Central

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

    2013-01-01

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

  12. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family

    PubMed Central

    Pathak, Anand; Seipel, Katja; Pemov, Alexander; Dewan, Ramita; Brown, Christina; Ravichandran, Sarangan; Luke, Brian T.; Malasky, Michael; Suman, Shalabh; Yeager, Meredith; Gatti, Richard A.; Caporaso, Neil E.; Mulvihill, John J.; Goldin, Lynn R.; Pabst, Thomas; McMaster, Mary L.; Stewart, Douglas R.

    2016-01-01

    Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia. PMID:26721895

  13. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family.

    PubMed

    Pathak, Anand; Seipel, Katja; Pemov, Alexander; Dewan, Ramita; Brown, Christina; Ravichandran, Sarangan; Luke, Brian T; Malasky, Michael; Suman, Shalabh; Yeager, Meredith; Gatti, Richard A; Caporaso, Neil E; Mulvihill, John J; Goldin, Lynn R; Pabst, Thomas; McMaster, Mary L; Stewart, Douglas R

    2016-07-01

    Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia. PMID:26721895

  14. Vaccines as consolidation therapy for myeloid leukemia

    PubMed Central

    Alatrash, Gheath; Molldrem, Jeffrey J

    2011-01-01

    Immunotherapy for myeloid leukemias remains a cornerstone in the management of this highly aggressive group of malignancies. Allogeneic (allo) stem cell transplantation (SCT), which can be curative in acute and chronic myeloid leukemias, exemplifies the success of immunotherapy for cancer management. However, because of its nonspecific immune response against normal tissue, allo-SCT is associated with high rates of morbidity and mortality, secondary to graft-versus-host disease, which can occur in up to 50% of allo-SCT recipients. Targeted immunotherapy using leukemia vaccines has been heavily investigated, as these vaccines elicit specific immune responses against leukemia cells while sparing normal tissue. Peptide and cellular vaccines have been developed against tumor-specific and leukemia-associated self-antigens. Although not yet considered the standard of care, leukemia vaccines continue to show promising results in the management of the myeloid leukemias. PMID:21322777

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

    ClinicalTrials.gov

    2016-03-14

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

  16. MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  17. Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

    PubMed

    Rosshandler, Yasmin; Shen, Ann Q; Cortes, Jorge; Khoury, Hanna Jean

    2016-05-01

    Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia. PMID:26853281

  18. Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-18

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

  19. Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

    PubMed Central

    de Rooij, Jasmijn D.E.; Beuling, Eva; van den Heuvel-Eibrink, Marry M.; Obulkasim, Askar; Baruchel, André; Trka, Jan; Reinhardt, Dirk; Sonneveld, Edwin; Gibson, Brenda E.S.; Pieters, Rob; Zimmermann, Martin; Zwaan, C. Michel; Fornerod, Maarten

    2015-01-01

    IKAROS family zinc finger 1/IKZF1 is a transcription factor important in lymphoid differentiation, and a known tumor suppressor in acute lymphoid leukemia. Recent studies suggest that IKZF1 is also involved in myeloid differentiation. To investigate whether IKZF1 deletions also play a role in pediatric acute myeloid leukemia, we screened a panel of pediatric acute myeloid leukemia samples for deletions of the IKZF1 locus using multiplex ligation-dependent probe amplification and for mutations using direct sequencing. Three patients were identified with a single amino acid variant without change of IKZF1 length. No frame-shift mutations were found. Out of 11 patients with an IKZF1 deletion, 8 samples revealed a complete loss of chromosome 7, and 3 cases a focal deletion of 0.1–0.9Mb. These deletions included the complete IKZF1 gene (n=2) or exons 1–4 (n=1), all leading to a loss of IKZF1 function. Interestingly, differentially expressed genes in monosomy 7 cases (n=8) when compared to non-deleted samples (n=247) significantly correlated with gene expression changes in focal IKZF1-deleted cases (n=3). Genes with increased expression included genes involved in myeloid cell self-renewal and cell cycle, and a significant portion of GATA target genes and GATA factors. Together, these results suggest that loss of IKZF1 is recurrent in pediatric acute myeloid leukemia and might be a determinant of oncogenesis in acute myeloid leukemia with monosomy 7 PMID:26069293

  20. Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-12-15

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

  1. Immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G

    2005-09-01

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

  2. Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-12-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  4. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

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

    ClinicalTrials.gov

    2013-01-04

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

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

    MedlinePlus

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

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

    MedlinePlus

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

  8. What Should You Ask Your Doctor about Chronic Myeloid Leukemia?

    MedlinePlus

    ... chronic myeloid leukemia? What should you ask your doctor about chronic myeloid leukemia? As you cope with ... need to have honest, open discussions with your doctor. You should feel free to ask any question ...

  9. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-05

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

  10. Oncogene Activation in Myeloid Leukemias by Graffi Murine Leukemia Virus Proviral Integration

    PubMed Central

    Denicourt, Catherine; Edouard, Elsy; Rassart, Eric

    1999-01-01

    The Graffi murine leukemia virus (MuLV) is a nondefective retrovirus that induces granulocytic leukemia in BALB/c and NFS mice. To identify genes involved in Graffi MuLV-induced granulocytic leukemia, tumor cell DNAs were examined for genetic alterations at loci described as common proviral integration sites in MuLV-induced myeloid, lymphoid, and erythroid leukemias. Southern blot analysis revealed rearrangements in c-myc, Fli-1, Pim-1, and Spi-1/PU.1 genes in 20, 10, 3.3, and 3.3% of the tumors tested, respectively. These results demonstrate for the first time the involvement of those genes in granulocytic leukemia. PMID:10196342

  11. Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

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

  12. Acute Myeloid Leukemia Presenting with Pulmonary Tuberculosis

    PubMed Central

    Thomas, Merlin; AlGherbawe, Mushtak

    2014-01-01

    We report the case of a 58-year-old immunocompetent man presenting with fever, cough, anorexia, weight loss, and cervical lymphadenopathy. Blood investigations revealed severe neutropenia with monocytosis. Chest imaging showed bilateral reticular infiltrates with mediastinal widening. Bronchoalveolar lavage culture and molecular test were positive for Mycobacterium tuberculosis and treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol was started. Although pulmonary tuberculosis could explain this clinical presentation we suspected associated blood dyscrasias in view of significant monocytosis and mild splenomegaly. Bone marrow aspiration revealed acute myeloid leukemia. Thereafter the patient received induction chemotherapy and continued antituberculous treatment. After first induction of chemotherapy patient was in remission and successfully completed 6 months antituberculosis therapy without any complications. To our knowledge there has been no such case reported from the State of Qatar to date. PMID:24987539

  13. Trisomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker.

    PubMed

    Saied, Marwa H; Marzec, Jacek; Khalid, Sabah; Smith, Paul; Molloy, Gael; Young, Bryan D

    2015-01-01

    Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI (P = 7.88 × 10(-11)) identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML. PMID:25674022

  14. Novel drug therapies in myeloid leukemia.

    PubMed

    Horne, Gillian A; Kinstrie, Ross; Copland, Mhairi

    2015-01-01

    Both acute myeloid leukemia and chronic myeloid leukemia are thought to arise from a subpopulation of primitive cells, termed leukemic stem cells that share properties with somatic stem cells. Leukemic stem cells are capable of continued self-renewal, and are resistant to conventional chemotherapy and are considered to be responsible for disease relapse. In recent years, improved understanding of the underlying mechanisms of myeloid leukemia biology has led to the development of novel and targeted therapies. This review focuses on clinically relevant patent applications and their relevance within the known literature in two areas of prevailing therapeutic interest, namely monoclonal antibody therapy and small molecule inhibitors in disease-relevant signaling pathways. PMID:26030080

  15. A Case of T-cell Acute Lymphoblastic Leukemia Relapsed As Myeloid Acute Leukemia.

    PubMed

    Paganin, Maddalena; Buldini, Barbara; Germano, Giuseppe; Seganfreddo, Elena; Meglio, Annamaria di; Magrin, Elisa; Grillo, Francesca; Pigazzi, Martina; Rizzari, Carmelo; Cazzaniga, Giovanni; Khiabanian, Hossein; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A; Basso, Giuseppe

    2016-09-01

    A 4-year-old male with the diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) relapsed after 19 months with an acute myeloid leukemia (AML). Immunoglobulin and T-cell receptor gene rearrangements analyses reveal that both leukemias were rearranged with a clonal relationship between them. Comparative genomic hybridization (Array-CGH) and whole-exome sequencing analyses of both samples suggest that this leukemia may have originated from a common T/myeloid progenitor. The presence of homozygous deletion of p16/INK4A, p14/ARF, p15/INK4B, and heterozygous deletion of WT1 locus remained stable in the leukemia throughout phenotypic switch, revealing that this AML can be genetically associated to T-ALL. PMID:27149388

  16. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  17. General Information about Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

    MedlinePlus

    ... Other Myeloid Malignancies Treatment (PDQ®)–Patient Version General Information About Childhood Acute Myeloid Leukemia and Other Myeloid ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  18. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    ClinicalTrials.gov

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; 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); Recurrent Adult Acute Myeloid Leukemia

  19. Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission

    ClinicalTrials.gov

    2016-06-27

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

  20. CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-23

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

  1. Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-04

    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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-01

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

  3. Differentiation Therapy of Acute Myeloid Leukemia

    PubMed Central

    Gocek, Elzbieta; Marcinkowska, Ewa

    2011-01-01

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML. PMID:24212816

  4. Chronic myeloid leukemia: reminiscences and dreams.

    PubMed

    Mughal, Tariq I; Radich, Jerald P; Deininger, Michael W; Apperley, Jane F; Hughes, Timothy P; Harrison, Christine J; Gambacorti-Passerini, Carlo; Saglio, Giuseppe; Cortes, Jorge; Daley, George Q

    2016-05-01

    With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic myeloid leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards. Then, in collaboration with Brian Druker, he led efforts to develop ABL1 tyrosine kinase inhibitors for the treatment of patients with chronic myeloid leukemia in the late 1990s. He also led the global efforts to develop and harmonize methodology for molecular monitoring, and was an indefatigable organizer of international conferences. These conferences brought together clinicians and scientists, and accelerated the adoption of new therapies. The abundance of praise, tributes and testimonies expressed by many serve to illustrate the indelible impressions these two passionate and affable scholars made on so many people's lives. This tribute provides an outline of the remarkable story of chronic myeloid leukemia, and in writing it, it is clear that the historical triumph of biomedical science over this leukemia cannot be considered without appreciating the work of both Janet Rowley and John Goldman. PMID:27132280

  5. Chronic myeloid leukemia: reminiscences and dreams

    PubMed Central

    Mughal, Tariq I.; Radich, Jerald P.; Deininger, Michael W.; Apperley, Jane F.; Hughes, Timothy P.; Harrison, Christine J.; Gambacorti-Passerini, Carlo; Saglio, Giuseppe; Cortes, Jorge; Daley, George Q.

    2016-01-01

    With the deaths of Janet Rowley and John Goldman in December 2013, the world lost two pioneers in the field of chronic myeloid leukemia. In 1973, Janet Rowley, unraveled the cytogenetic anatomy of the Philadelphia chromosome, which subsequently led to the identification of the BCR-ABL1 fusion gene and its principal pathogenetic role in the development of chronic myeloid leukemia. This work was also of major importance to support the idea that cytogenetic changes were drivers of leukemogenesis. John Goldman originally made seminal contributions to the use of autologous and allogeneic stem cell transplantation from the late 1970s onwards. Then, in collaboration with Brian Druker, he led efforts to develop ABL1 tyrosine kinase inhibitors for the treatment of patients with chronic myeloid leukemia in the late 1990s. He also led the global efforts to develop and harmonize methodology for molecular monitoring, and was an indefatigable organizer of international conferences. These conferences brought together clinicians and scientists, and accelerated the adoption of new therapies. The abundance of praise, tributes and testimonies expressed by many serve to illustrate the indelible impressions these two passionate and affable scholars made on so many people’s lives. This tribute provides an outline of the remarkable story of chronic myeloid leukemia, and in writing it, it is clear that the historical triumph of biomedical science over this leukemia cannot be considered without appreciating the work of both Janet Rowley and John Goldman. PMID:27132280

  6. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

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

  7. Acute myeloid leukemia developing in patients with autoimmune diseases

    PubMed Central

    Ramadan, Safaa M.; Fouad, Tamer M; Summa, Valentina; Hasan, Syed KH; Lo-Coco, Francesco

    2012-01-01

    Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for patients with highly curable primary malignancies and favorable life expectancy. The risk of developing therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with autoimmune diseases compared to the general population, with a further increase in risk after exposure to cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia development and exposure to individual agents used for the treatment of autoimmune diseases. Given the dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune diseases who are exposed to cytotoxic agents as ‘therapy-related leukemias’. A better understanding of the molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better understanding of the association between these two diseases entities. PMID:22180424

  8. Molecular dysfunctions in acute myeloid leukemia revealed by integrated analysis of microRNA and transcription factor.

    PubMed

    Lin, Xiao-Cong; Xu, Yong; Sun, Guo-Ping; Wen, Jin-Li; Li, Ning; Zhang, Yu-Ming; Yang, Zhi-Gang; Zhang, Hai-Tao; Dai, Yong

    2016-06-01

    Acute myeloid leukemia (AML) is a heterogenic hematological malignancy with pathogenesis that has yet to be elucidated. MicroRNAs (miRNAs) and transcription factors (TFs) are two major regulators of gene expression, which may play important roles in the etiology of AML. However, the global regulation of gene expression in AML, involving miRNAs and TFs, still remains elusive. To characterize the global role of miRNAs and TFs in AML pathogenesis, large scale expression profiling of miRNA and TF was performed using miRNA sequencing and TF array technology, respectively, and validated by qPCR. In the present study, 308 miRNAs and 84 TFs were identified to be differentially expressed (fold-change ≥2.0) in AML samples relative to their controls. After integrating the expression profiling data into bioinformatic analysis, we identified 1,462 miRNA-gene pairs, 982 TF-gene pairs and 296 TF-miRNA pairs. By merging these regulatory relations together, we constructed a comprehensive AML-specific miRNA-TF regulatory network. In this network, we identified 22 hub miRNAs and 11 hub TFs. KEGG pathway analysis showed that the network nodes were significantly enriched in 33 different pathways, of which the AML pathway was the most significant. After analyzing the topology of the subnetwork, we propose that TCF3 was a potential key regulator in this regulatory network. In conclusion, this is the first study perform on global expression profiling of miRNAs and TFs relating to AML. These results may enhance our understanding of the molecular mechanisms underlying AML and provide potential targets for future therapeutics. PMID:27082628

  9. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2015-03-02

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

  10. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  11. Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-05-17

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

  13. Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-02-17

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

  14. Functional phosphoproteomic analysis reveals cold-shock domain protein A to be a Bcr-Abl effector-regulating proliferation and transformation in chronic myeloid leukemia

    PubMed Central

    Sears, D; Luong, P; Yuan, M; Nteliopoulos, G; Man, Y K S; Melo, J V; Basu, S

    2010-01-01

    One proposed strategy to suppress the proliferation of imatinib-resistant cells in chronic myeloid leukemia (CML) is to inhibit key proteins downstream of Bcr-Abl. The PI3K/Akt pathway is activated by Bcr-Abl and is specifically required for the growth of CML cells. To identify targets of this pathway, we undertook a proteomic screen and identified several proteins that differentially bind 14-3-3, dependent on Bcr-Abl kinase activity. An siRNA screen of candidates selected by bioinformatics analysis reveals cold-shock domain protein A (CSDA), shown previously to regulate cell cycle progression in epithelial cells, to be a positive regulator of proliferation in a CML cell line. We show that Akt can phosphorylate the serine 134 residue of CSDA but, downstream of Bcr-Abl activity, this modification is mediated through the activation of MEK/p90 ribosomal S6 kinase (RSK) signaling. Inhibition of RSK, similarly to treatment with imatinib, blocked proliferation specifically in Bcr-Abl-positive leukemia cell lines, as well as cells from CML patients. Furthermore, these primary CML cells showed an increase in CSDA phosphorylation. Expression of a CSDA phospho-deficient mutant resulted in the decrease of Bcr-Abl-dependent transformation in Rat1 cells. Our results support a model whereby phosphorylation of CSDA downstream of Bcr-Abl enhances proliferation in CML cells to drive leukemogenesis. PMID:21368869

  15. Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

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

    ClinicalTrials.gov

    2013-01-23

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

  17. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-01-07

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

  18. Acute Myeloid Leukemia: A Concise Review

    PubMed Central

    Saultz, Jennifer N.; Garzon, Ramiro

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Cytogenetics and mutation testing remain a critical prognostic tool for post induction treatment. Despite rapid advances in the field including new drug targets and increased understanding of the biology, AML treatment remains unchanged for the past three decades with the majority of patients eventually relapsing and dying of the disease. Allogenic transplant remains the best chance for cure for patients with intermediate or high risk disease. In this review, we discuss the landmark genetic studies that have improved outcome prediction and novel therapies. PMID:26959069

  19. Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2016-03-30

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

  20. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-01-06

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

  1. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-08

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

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

    ClinicalTrials.gov

    2015-06-03

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

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

    ClinicalTrials.gov

    2016-04-05

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

  4. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-03-16

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  5. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    MedlinePlus

    ... one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In ... 1 link) PubMed Sources for This Page Döhner H. Implication of the molecular characterization of acute myeloid ...

  6. What Are the Risk Factors for Chronic Myeloid Leukemia?

    MedlinePlus

    ... of an atomic bomb blast or nuclear reactor accident) increases the risk of getting CML Age : The ... Myeloid (CML)? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Leukemia - Chronic Myeloid (CML) ...

  7. Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-19

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  8. High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy

    PubMed Central

    Ferrell, Paul Brent; Diggins, Kirsten Elizabeth; Polikowsky, Hannah Grace; Mohan, Sanjay Ram; Seegmiller, Adam C.

    2016-01-01

    The plasticity of AML drives poor clinical outcomes and confounds its longitudinal detection. However, the immediate impact of treatment on the leukemic and non-leukemic cells of the bone marrow and blood remains relatively understudied. Here, we conducted a pilot study of high dimensional longitudinal monitoring of immunophenotype in AML. To characterize changes in cell phenotype before, during, and immediately after induction treatment, we developed a 27-antibody panel for mass cytometry focused on surface diagnostic markers and applied it to 46 samples of blood or bone marrow tissue collected over time from 5 AML patients. Central goals were to determine whether changes in AML phenotype would be captured effectively by cytomic tools and to implement methods for describing the evolving phenotypes of AML cell subsets. Mass cytometry data were analyzed using established computational techniques. Within this pilot study, longitudinal immune monitoring with mass cytometry revealed fundamental changes in leukemia phenotypes that occurred over time during and after induction in the refractory disease setting. Persisting AML blasts became more phenotypically distinct from stem and progenitor cells due to expression of novel marker patterns that differed from pre-treatment AML cells and from all cell types observed in healthy bone marrow. This pilot study of single cell immune monitoring in AML represents a powerful tool for precision characterization and targeting of resistant disease. PMID:27074138

  9. Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders

    ClinicalTrials.gov

    2016-07-20

    Accelerated Phase of Disease; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase of Disease; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Recurrent Disease

  10. Targeting chronic myeloid leukemia stem cells.

    PubMed

    Kinstrie, Ross; Copland, Mhairi

    2013-03-01

    Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of the fusion oncogene BCR-ABL that encodes the tyrosine kinase BCR-ABL. Constitutive expression of BCR-ABL leads to the unregulated production of mature myeloid cells in the bone marrow and their subsequent release into the blood. Untreated, CML will progress from a chronic to accelerated phase over a number of years before quickly proceeding to a terminal blast crisis phase, reminiscent of acute leukemia. The advent of tyrosine kinase inhibitors has led to much improved management of the disease, but these drugs do not provide a cure as they are unable to eradicate the most primitive, quiescent fraction of CML stem cells. This review looks at recent research into targeting CML stem cells and focuses on major signalling pathways of interest. PMID:23264204

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

    ClinicalTrials.gov

    2015-08-29

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

  12. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia

    PubMed Central

    Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich

    2016-01-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [68Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche. PMID:27175029

  13. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia.

    PubMed

    Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich

    2016-08-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [(68)Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche. PMID:27175029

  14. Acute myeloid leukemia masquerading as hepatocellular carcinoma

    PubMed Central

    Abu-Zeinah, Ghaith F.; Weisman, Paul; Ganesh, Karuna; Katz, Seth S.; Dogan, Ahmet; Abou-Alfa, Ghassan K.; Stein, Eytan M.; Jarnagin, William; Mauro, Michael J.

    2016-01-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient’s liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  15. Acute myeloid leukemia masquerading as hepatocellular carcinoma.

    PubMed

    Abu-Zeinah, Ghaith F; Weisman, Paul; Ganesh, Karuna; Katz, Seth S; Dogan, Ahmet; Abou-Alfa, Ghassan K; Stein, Eytan M; Jarnagin, William; Mauro, Michael J; Harding, James J

    2016-06-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient's liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  16. Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse.

    PubMed

    Farrar, Jason E; Schuback, Heather L; Ries, Rhonda E; Wai, Daniel; Hampton, Oliver A; Trevino, Lisa R; Alonzo, Todd A; Guidry Auvil, Jaime M; Davidsen, Tanja M; Gesuwan, Patee; Hermida, Leandro; Muzny, Donna M; Dewal, Ninad; Rustagi, Navin; Lewis, Lora R; Gamis, Alan S; Wheeler, David A; Smith, Malcolm A; Gerhard, Daniela S; Meshinchi, Soheil

    2016-04-15

    The genomic and clinical information used to develop and implement therapeutic approaches for acute myelogenous leukemia (AML) originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative used whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML. One hundred forty-five somatic variants at diagnosis (median 6 mutations/patient) and 149 variants at relapse (median 6.5 mutations) were identified and verified by orthogonal methodologies. Recurrent somatic variants [in (greater than or equal to) 2 patients] were identified for 10 genes (FLT3, NRAS, PTPN11, WT1, TET2, DHX15, DHX30, KIT, ETV6, KRAS), with variable persistence at relapse. The variant allele fraction (VAF), used to measure the prevalence of somatic mutations, varied widely at diagnosis. Mutations that persisted from diagnosis to relapse had a significantly higher diagnostic VAF compared with those that resolved at relapse (median VAF 0.43 vs. 0.24, P < 0.001). Further analysis revealed that 90% of the diagnostic variants with VAF >0.4 persisted to relapse compared with 28% with VAF <0.2 (P < 0.001). This study demonstrates significant variability in the mutational profile and clonal evolution of pediatric AML from diagnosis to relapse. Furthermore, mutations with high VAF at diagnosis, representing variants shared across a leukemic clonal structure, may constrain the genomic landscape at relapse and help to define key pathways for therapeutic targeting. Cancer Res; 76(8); 2197-205. ©2016 AACR. PMID:26941285

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

    ClinicalTrials.gov

    2016-07-20

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

  18. Management of acute myeloid leukemia during pregnancy.

    PubMed

    Avivi, Irit; Brenner, Benjamin

    2014-06-01

    Diagnosis of acute leukemia during pregnancy presents significant medical challenges. Pancytopenia, caused by bone marrow substitution with leukemic cells, impairs maternal and fetal health. Chemotherapeutic agents required to be immediately used to save the mother's life are likely to adversely affect fetal development and outcome, especially if administered at an early gestational stage. Patients diagnosed with acute leukemia during the first trimester are, therefore, recommended to undergo pregnancy termination. At later gestational stages, antileukemic therapy can be administered, although in this case, fetal outcome is still associated with increased incidence of growth restriction and loss. Special attention to the issue of future reproduction, adopting a personalized fertility preservation approach, is required. This article addresses these subjects, presenting women diagnosed with acute myeloid and acute promyelocytic leukemia in pregnancy. The rarity of this event, resulting in insufficient data, emphasizes the need for collaborative efforts to optimize management of this complicated clinical condition. PMID:25052751

  19. Targeting MTHFD2 in acute myeloid leukemia.

    PubMed

    Pikman, Yana; Puissant, Alexandre; Alexe, Gabriela; Furman, Andrew; Chen, Liying M; Frumm, Stacey M; Ross, Linda; Fenouille, Nina; Bassil, Christopher F; Lewis, Caroline A; Ramos, Azucena; Gould, Joshua; Stone, Richard M; DeAngelo, Daniel J; Galinsky, Ilene; Clish, Clary B; Kung, Andrew L; Hemann, Michael T; Vander Heiden, Matthew G; Banerji, Versha; Stegmaier, Kimberly

    2016-06-27

    Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. PMID:27325891

  20. Acute myeloid leukemia: advances in diagnosis and classification.

    PubMed

    Hasserjian, R P

    2013-06-01

    Acute myeloid leukemia is an aggressive myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute myeloid leukemia are based on both patient-related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute myeloid leukemia and their influence on prognosis. Future therapies for acute myeloid leukemia will increasingly rely on the genetic signatures of individual leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute myeloid leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans. PMID:23590662

  1. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  2. CCI-779 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, or Chronic Myelogenous Leukemia in Blastic Phase

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

  3. Intracellular markers in acute myeloid leukemia diagnosis.

    PubMed

    Koníková, E; Glasová, M; Kusenda, J; Babusíková, O

    1998-01-01

    In our study we used a new proposed system of CD45 monoclonal antibody in combination with the side scatter (SSC) parameter as a very useful gating method allowing myeloblast detection especially in cases with low blasts percentage in examined samples. Immunological demonstration of myeloperoxidase (MPO) in the cytoplasm of AML blasts is considered to be a reliable and highly sensitive marker. Using a direct single and double immunofluorescence staining method and flow cytometry we evaluated the intracellular expression of two granular constituents of myeloid cells--MPO and lactoferrin (LF) in leukemia cells from 18 patients at AML diagnosis, two patients in remission after allogenic bone marrow transplantation and in six controls. Two different fixation/permeabilization techniques were used: Fix&Perm, paraformaldehyde and saponin prior to monoclonal antibody staining in order to verify the sensitivity of two labeling methods for MPO. Although both reagents used in this study proved to be efficient tools for the fixation and permeabilization of leukemia cells, the second one was characterized by higher sensitivity in detection of MPO. By double staining of MPO and LF we were able to distinguish undifferentiated cells from the granulomonocytic maturation compartments in bone marrow, since LF is proposed to be selectively expressed from the myelocyte stage of differentiation onward. Cytoplasmic CD13 expression was detectable in AML blasts after their buffered-formaldehyde-acetone fixation/permeabilization. According to our results the detection of MPO and CD13 markers in the cytoplasm of leukemia cells is of great importance in the definition of FAB M0-M1 subtype of AML. Furthermore we described overexpression of CD34 antigen in AML and revealed the characteristic marker combination when CD34 was studied simultaneously with MPO. This finding also coincided with some atypical phenotypic features (CD15/MPO, CD7/cCD13, CD2/cCD13, CD33/cCD13, MPO/cCD13) contributing to

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

    ClinicalTrials.gov

    2016-07-25

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

  5. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2015-07-14

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

  7. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

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

  8. Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-27

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  9. WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-01-25

    Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Hematopoietic Differentiation Is Required for Initiation of Acute Myeloid Leukemia.

    PubMed

    Ye, Min; Zhang, Hong; Yang, Henry; Koche, Richard; Staber, Philipp B; Cusan, Monica; Levantini, Elena; Welner, Robert S; Bach, Christian S; Zhang, Junyan; Krivtsov, Andrei V; Armstrong, Scott A; Tenen, Daniel G

    2015-11-01

    Mutations in acute myeloid leukemia (AML)-associated oncogenes often arise in hematopoietic stem cells (HSCs) and promote acquisition of leukemia stem cell (LSC) phenotypes. However, as LSCs often share features of lineage-restricted progenitors, the relative contribution of differentiation status to LSC transformation is unclear. Using murine MLL-AF9 and MOZ-TIF2 AML models, we show that myeloid differentiation to granulocyte macrophage progenitors (GMPs) is critical for LSC generation. Disrupting GMP formation by deleting the lineage-restricted transcription factor C/EBPa blocked normal granulocyte formation and prevented initiation of AML. However, restoring myeloid differentiation in C/EBPa mutants with inflammatory cytokines reestablished AML transformation capacity. Genomic analyses of GMPs, including gene expression and H3K79me2 profiling in conjunction with ATAC-seq, revealed a permissive genomic environment for activation of a minimal transcription program shared by GMPs and LSCs. Together, these findings show that myeloid differentiation is a prerequisite for LSC formation and AML development, providing insights for therapeutic development. PMID:26412561

  11. Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Targeting the Microenvironment in Acute Myeloid Leukemia

    PubMed Central

    Rashidi, Armin; Uy, Geoffrey L.

    2015-01-01

    The bone marrow microenvironment plays a critical role in the development, progression, and relapse of acute myeloid leukemia (AML). Similar to normal hematopoietic stem cells, AML blasts express receptors on their surface, allowing them to interact with specific components of the marrow microenvironment. These interactions contribute to both chemotherapy resistance and disease relapse. Preclinical studies and early phase clinical trials have demonstrated the potential for targeting the tumor-microenvironment interactions in AML. Agents currently under investigation include hypoxia-inducible agents and inhibitors of CXCR4 and adhesion molecules such as VLA-4 and E-selectin. PMID:25921388

  13. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-04-03

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-12

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

  15. Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-05

    Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1; Acute Myeloid Leukemia With a Variant RARA Translocation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Acute Myeloid Leukemia With Variant MLL Translocations; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2013-09-27

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

  17. Chronic myeloid leukemia with monoclonal gammopathy terminating in myeloid crisis and immunoblastic lymphoma.

    PubMed

    Larocca, L M; Zollino, M; Carbone, A; Eboli, M L; Mango, G; Leone, G

    1989-04-30

    A patient, with chronic myeloid leukemia and IgA monoclonal gammopathy, who contemporaneously developed myeloid blast crisis and immunoblastic lymphoma is reported. Cytogenetic studies showed complex chromosome abnormalities concerning chromosomes 8, 14 and 22, other than the Ph chromosome. A possible relationship between the emergence of immunoblasts from slow proliferating lymphoplasmacytoid cells, myeloid blasts crisis and chromosomal changes is discussed. PMID:2741214

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

    ClinicalTrials.gov

    2016-06-24

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

  19. Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

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

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

    ClinicalTrials.gov

    2014-09-04

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

  1. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2011-11-03

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

  2. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-13

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

  3. CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-04-25

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  4. AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-23

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

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

    ClinicalTrials.gov

    2016-03-16

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

  6. Therapeutic Autologous Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2011-07-12

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  7. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-07-26

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

  8. Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia

    PubMed Central

    Chen, Yaoyu; Li, Shaoguang

    2014-01-01

    In a significant proportion of patients with chronic myeloid leukemia, resistance to BCR-ABL tyrosine kinase inhibitors develops due to acquisition of BCR-ABL kinase domain mutations and insensitivity of leukemia stem cells to tyrosine kinase inhibitors. Omacetaxine mepesuccinate (formerly called homoharringtonine) is a natural alkaloid that inhibits protein synthesis and induces cell death. Omacetaxine mepesuccinate has been recently approved by the US Food and Drug Administration to treat patients with chronic myeloid leukemia who failed to respond to multiple tyrosine kinase inhibitors and/or acquired the BCR-ABL-T315I mutation. In this review, we discuss the use and effectiveness of omacetaxine mepesuccinate in the treatment of chronic myeloid leukemia, with coverage of its pharmacology, mode of action, and pharmacokinetics. We believe that omacetaxine mepesuccinate will be beneficial to many patients with chronic myeloid leukemia who do not respond well to tyrosine kinase inhibitors. PMID:24516334

  9. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-22

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  11. Induction of Chronic Myeloid Leukemia in Mice.

    PubMed

    Zhang, Haojian; Li, Shaoguang

    2016-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder derived from a hematopoietic stem cell (HSC), harboring Philadelphia chromosome (Ph chromosome). Formation of the Ph chromosome is caused by a reciprocal translocation between the chromosomes 9 and 22 t(9;22)(q34;q11), resulting in a fusion protein known as BCR-ABL which has constitutive tyrosine kinase activity and promotes the proliferation of leukemia cells via multiple mechanisms. Studies on CML have led to the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It has become clear that leukemia stem cells (LSCs) in CML are insensitive to inhibition by TKIs, and eradication of LSCs appears to be difficult. Therefore, some of the major issues in current CML therapy are to understand the biology of LSCs and to investigate why LSCs are insensitive to TKIs for developing curative therapeutic strategies. In this regard, application of mouse models recapitulating human CML disease will be critical. In this chapter, we describe methods for induction of CML in mice with BCR-ABL. PMID:27581135

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

    ClinicalTrials.gov

    2013-09-27

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

  13. Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

    MedlinePlus

    ... N. A family harboring a germ-line N-terminal C/EBPalpha mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPalpha mutation. Genes Chromosomes Cancer. 2010 Mar; ...

  14. Comparative proteomics in acute myeloid leukemia

    PubMed Central

    Luczak, Magdalena; Kaźmierczak, Maciej; Hadschuh, Luiza; Lewandowski, Krzysztof; Komarnicki, Mieczysław

    2012-01-01

    The term proteomics was used for the first time in 1995 to describe large-scale protein analyses. At the same time proteomics was distinguished as a new domain of the life sciences. The major object of proteomic studies is the proteome, i.e. the set of all proteins accumulating in a given cell, tissue or organ. During the last years several new methods and techniques have been developed to increase the fidelity and efficacy of proteomic analyses. The most widely used are two-dimensional electrophoresis (2DE) and mass spectrometry (MS). In the past decade proteomic analyses have also been successfully applied in biomedical research. They allow one to determine how various diseases affect the pattern of protein accumulation. In this paper, we attempt to summarize the results of the proteomic analyses of acute myeloid leukemia (AML) cells. They have increased our knowledge on the mechanisms underlying AML development and contributed to progress in AML diagnostics and treatment. PMID:23788862

  15. Monitoring Molecular Response in Chronic Myeloid Leukemia

    PubMed Central

    Cortes, Jorge; Quintás-Cardama, Alfonso; Kantarjian, Hagop M.

    2016-01-01

    Background Prior to the advent of tyrosine kinase inhibitor (TKI) therapy, the evaluation of hematologic and cytogenetic responses was sufficient to gauge treatment efficacy in patients with chronic myeloid leukemia. However, with more potent TKI therapies, the majority of patients achieve complete cytogenetic response (CCyR). Furthermore, deeper molecular responses are now commonly achieved, necessitating a reliance on molecular monitoring to assess residual leukemic disease. Methods/Results The prognostic significance between molecular responses and duration of CCyR, progression-free survival, and event-free survival is described herein. A discussion of the concept of complete molecular response is also provided and the potential for imatinib treatment discontinuation is evaluated. The implications of rising BCR-ABL1 transcript levels and caveats of molecular monitoring are also described. PMID:20960522

  16. Total body irradiation in chronic myeloid leukemia

    SciTech Connect

    Advani, S.H.; Dinshaw, K.A.; Nair, C.N.; Ramakrishnan, G.

    1983-04-01

    Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following vusulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.

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

    ClinicalTrials.gov

    2013-07-03

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

  18. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-10-19

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

  19. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-03

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

  20. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    ClinicalTrials.gov

    2015-06-18

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

  1. Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-04

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  2. Acute myeloid leukemia in the older patient.

    PubMed

    Godwin, John E; Smith, Scott E

    2003-10-15

    Acute myeloid leukemia (AML) is an extremely heterogeneous disorder. The biology of AML is incompletely understood, but much data indicates that older patients have a more biologically diverse and chemotherapy resistant form of AML that is quite different from that seen in the younger patients. Approximately 60% of AML cases are in patients greater than 60 years of age, so the predominant burden is in older patients. This problem will be magnified in the future, because the US population is both growing and aging. When one examines the treatment outcomes of older AML patients over the last three decades, there is little progress in long-term survival. Nine major published randomized placebo controlled trials of myeloid growth factors given during induction for AML have been conducted. All of these trials with one exception demonstrated no significant impact on the clinical outcomes of complete response (CR) rate, disease-free, and overall survival. However, the duration of neutropenia was consistently and uniformly reduced by the use of growth factor in all nine of these trials. Because of the favorable impact of the colony-stimulating factors (CSFs) on resource use, antibiotic days, hospital days, etc., it can be more economical and beneficial to use CSFs in AML than to withhold use. The overall dismal outlook for the older AML patient can only be altered by clinical trials with new therapeutic agents. New cellular and molecularly targeted agents are entering clinical trials and bring hope for progress to this area of cancer therapy. PMID:14563517

  3. Novel and Emerging Drugs for Acute Myeloid Leukemia

    PubMed Central

    Stein, E.M.; Tallman, M.S.

    2014-01-01

    Acute myeloid leukemia (AML) is a challenging disease to treat with the majority of patients dying from their illness. While overall survival has been markedly prolonged in acute promyelocytic leukemia (APL), survival in younger adults with other subtypes of AML has only modestly improved over the last twenty years. Physicians who treat AML eagerly await drugs like Imatinib for chronic myeloid leukemia, Cladribine for hairy cell leukemia, and Rituximab for non-Hodgkin Lymphoma which have had an important impact on improving outcome. Recent research efforts have focused on refining traditional chemotherapeutic agents to make them more active in AML, targeting specific genetic mutations in myeloid leukemia cells, and utilizing novel agents such as Lenalidomide that have shown activity in other hematologic malignancies. Here, we focus on reviewing the recent literature on agents that may assume a role in clinical practice for patients with AML over the next five years. PMID:22483153

  4. Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-19

    Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Untreated Adult Acute Myeloid Leukemia

  5. Acute myeloid leukemia in the vascular niche.

    PubMed

    Cogle, Christopher R; Bosse, Raphael C; Brewer, Takae; Migdady, Yazan; Shirzad, Reza; Kampen, Kim Rosalie; Saki, Najmaldin

    2016-10-01

    The greatest challenge in treating acute myeloid leukemia (AML) is refractory disease. With approximately 60-80% of AML patients dying of relapsed disease, there is an urgent need to define and target mechanisms of drug resistance. Unfortunately, targeting cell-intrinsic resistance has failed to improve clinical outcomes in AML. Emerging data show that cell-extrinsic factors in the bone marrow microenvironment protect and support AML cells. The vascular niche, in particular, regulates AML cell survival and cell cycling by both paracrine secretion and adhesive contact with endothelial cells. Moreover, AML cells can functionally integrate within vascular endothelia, undergo quiescence, and resist cytotoxic chemotherapy. Together, these findings support the notion of blood vessels as sanctuary sites for AML. Therefore, vascular targeting agents may serve to remit AML. Several early phase clinical trials have tested anti-angiogenic agents, leukemia mobilizing agents, and vascular disrupting agents in AML patients. In general, these agents can be safely administered to AML patients and cardiovascular side effects were reported. Response rates to vascular targeting agents in AML have been modest; however, a majority of vascular targeting trials in AML are monotherapy in design and indiscriminate in patient recruitment. When considering the chemosensitizing effects of targeting the microenvironment, there is a strong rationale to build upon these early phase clinical trials and initiate phase IB/II trials of combination therapy where vascular targeting agents are positioned as priming agents for cytotoxic chemotherapy. PMID:25963886

  6. Key Data Elements in Myeloid Leukemia.

    PubMed

    Varghese, Julian; Holz, Christian; Neuhaus, Phillip; Bernardi, Massimo; Boehm, Alexandra; Ganser, Arnold; Gore, Steven; Heaney, Mark; Hochhaus, Andreas; Hofmann, Wolf-Karsten; Krug, Utz; Müller-Tidow, Carsten; Smith, Alexandra; Weltermann, Ansgar; de Witte, Theo; Hehlmann, Rüdiger; Dugas, Martin

    2016-01-01

    Data standards consisting of key data elements for clinical routine and trial documentation harmonize documentation within and across different health care institutions making documentation more efficient and improving scientific data analysis. This work focusses on the field of myeloid leukemia (ML), where a semantic core of common data elements (CDEs) in routine and trial documentation is established by automatic UMLS-based form analysis of existing documentation models. These CDEs (n = 227) were initially reviewed and commented by leukemia experts before they were systematically surveyed by an international voting process through seven hematologists of four countries. The total agreement score was 86%. 116 elements (51%) of these share an agreement score of 100%. This work generated CDEs with language-independent semantic codes and international clinical expert review to build a first approach towards an international data standard for ML. A first version of the CDE list is implemented in the data standard Operational Data Model and additional other data formats for reuse in different medical information systems. PMID:27577388

  7. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    PubMed Central

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis. PMID:25885427

  8. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-10

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

  9. Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-09-18

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

  10. Adult Acute Myeloid Leukemia Long-term Survivors

    PubMed Central

    Cheng, M. Jennifer; Hourigan, Christopher S.; Smith, Thomas J.

    2014-01-01

    The number of leukemia patients and survivors is growing. This review summarizes what is known regarding the health related quality of life (HRQOL) and medical complications associated with acute myeloid leukemia (AML) disease and treatment and highlights understudied aspects of adult AML survivorship care, and potential novel areas for intervention. PMID:25243197

  11. Report of an Unusual Case: Testicular Involvement of Chronic Myeloid Leukemia 10 Years after the Complete Response

    PubMed Central

    Ozgur, Berat Cem; Sarici, Hasmet; Borcek, Pelin; Telli, Onur

    2014-01-01

    Testicular extra-medullary myeloid cell tumours are rare tumours presenting in most cases with painless testicular swelling. We are representing here along of a case of 21-year-old man with painless scrotal swelling. From his medical history, he was treated by allogenic bone-marrow transplantation and chemotherapy 10 years ago because of chronic myeloid leukemia. The pathology of orchiectomy specimen revealed malign cells with blastic cell infiltration means a late relapse of chronic myeloid leukemia. The patient has been in hematological remission and no evidence of any myeloid disorders by 10 years’ follow up. Although testicular involvement is a rare and an unusual event in blast crisis of chronic myeloid leukemia, extramedullary myeloid cell tumour should be considered in the diagnosis of intratesticular tumours. PMID:24959476

  12. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-08-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  13. Vorinostat and Azacitidine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-27

    Acute Erythroid Leukemia; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ring Sideroblasts

  14. Ruxolitinib induces autophagy in chronic myeloid leukemia cells.

    PubMed

    Bagca, Bakiye Goker; Ozalp, Ozgun; Kurt, Cansu Caliskan; Mutlu, Zeynep; Saydam, Guray; Gunduz, Cumhur; Avci, Cigir Biray

    2016-02-01

    Ruxolitinib is the first agent used in myelofibrosis treatment with its potent JAK2 inhibitory effect. In this novel study, we aimed to discover the anti-leukemic effect of ruxolitinib in K-562 human chronic myeloid leukemia cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. Cytotoxic effect of ruxolitinib was determined by using WST-1 assay. IC50 values for K-562 and NCI-BL 2171 cell lines were defined as 20 and 23.6 μM at the 48th hour, respectively. Autophagic effects of ruxolitinib were detected by measuring LC3B-II protein formation. Ruxolitinib induced autophagic cell death in K-562 and NCI-BL 2171 cell lines 2.11- and 1.79-fold compared to control groups, respectively. To determine the autophagy-related gene expression changes, total RNA was isolated from K-562 and NCI-BL 2171 cells treated with ruxolitinib and untreated cells as control group. Reverse transcription procedure was performed for cDNA synthesis, and gene expressions were shown by RT-qPCR. Ruxolitinib treatment caused a notable decrease in expression of AKT, mTOR, and STAT autophagy inhibitor genes in K-562 cells, contrariwise control cell line. Ruxolitinib is a promising agent in chronic myeloid leukemia treatment by blocking JAK/STAT pathway known as downstream of BCR-ABL and triggering autophagy. This is the first study that reveals the relationship between ruxolitinib and autophagy induction. PMID:26298727

  15. Cross-protective murine graft-versus-leukemia responses to phenotypically distinct myeloid leukemia lines.

    PubMed

    Patterson, A E; Korngold, R

    2000-01-01

    A c-myc retrovirus-transformed myeloid leukemia line, MMB3.19, of C57BL/6 (B6) origin, was developed to investigate graft-versus-leukemia (GVL) activity in murine bone marrow transplantation (BMT) models. It was previously determined that both naive and leukemia-presensitized CD4+-enriched T cells are capable of mediating GVL activity to MMB3.19 challenge in both syngeneic (B6) and allogeneic (C3H.SW-->B6) strain combinations, with the latter coinciding with minimal graft-versus-host disease. In the present study, MMB3.19 and 2 other similarly derived, yet phenotypically diverse, B6 myeloid leukemia lines (MMB1.10 and MMB2.18) were investigated for potential shared tumor antigens in the syngeneic GVL model. Morphologically, all 3 tumor lines are blastic with high cytoplasmic:nuclear ratios, but MMB2.18 displays dendritic processes, whereas MMB1.10 and MMB3.19 have a more rounded appearance. Flow cytometric analysis of the 3 lines revealed constitutive surface molecule expression of Mac-1, Mac-2, F4/80, LFA-1, B7-1, B7-2, H2Kb, H2Db, and macrophage scavenger receptor, consistent with macrophage/monocyte lineages. Furthermore, each of the lines expresses H2I-Ab, but to varying degrees, with MMB2.18 cells having the lowest percentage (31.6%). In vitro 51Cr release assays using MMB3.19-primed T-cell effectors demonstrated equivalent specific lysis of all 3 leukemia-line target cells. In addition, enzyme-linked immunospot analysis of MMB3.19-primed CD4+ T cells revealed significantly increased frequencies of tumor-stimulated interleukin (IL)-2-, IL-4-, and interferon-gamma-secreting cells when restimulated with each of the 3 leukemia lines. Furthermore, when MMB3.19-primed CD4+ T cells were administered in a BMT setting, a protective GVL effect was seen in those mice challenged with MMB1.10, MMB2.18, or MMB3.19. Therefore, in vitro and in vivo experiments indicate that the 3 distinct myeloid leukemia lines share 1 or more common major histocompatibility complex class II

  16. Perinatal risk factors for acute myeloid leukemia.

    PubMed

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2015-12-01

    Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P < 0.001), with peak risk among persons born in winter. Relative to persons born in summer (June-August), incidence rate ratios for AML were 1.72 (95 % CI 1.25-2.38; P = 0.001) for winter (December-February), 1.37 (95 % CI 0.99-1.90; P = 0.06) for spring (March-May), and 1.27 (95 % CI 0.90-1.80; P = 0.17) for fall (September-November). Other risk factors for AML included high fetal growth, high gestational age at birth, and low maternal education level. These findings did not vary by sex or age at diagnosis. Sex, birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML. PMID:26113060

  17. Myeloid Sarcoma in an Eyelid That Developed during Chemotherapy for Acute Myeloid Leukemia.

    PubMed

    Kang, Hyera; Takahashi, Yasuhiro; Takahashi, Emiko; Kakizaki, Hirohiko

    2016-01-01

    An 80-year-old female presented with a mass in the left upper eyelid margin that had developed during chemotherapy for acute myeloid leukemia. The mass was elastic, hard, and pinkish, with a relatively smooth surface but without madarosis. The histopathological findings corresponded to a myeloid sarcoma. No blast cells were shown in the peripheral blood at the time of biopsy, and she subsequently underwent an azacitidine injection regimen. The size of the eyelid tumor decreased 3 months after the biopsy, when the course of azacitidine injections was completed. However, acute myeloid leukemia recurred, and the patient died. PMID:26889156

  18. Myeloid Sarcoma in an Eyelid That Developed during Chemotherapy for Acute Myeloid Leukemia

    PubMed Central

    Kang, Hyera; Takahashi, Yasuhiro; Takahashi, Emiko; Kakizaki, Hirohiko

    2016-01-01

    An 80-year-old female presented with a mass in the left upper eyelid margin that had developed during chemotherapy for acute myeloid leukemia. The mass was elastic, hard, and pinkish, with a relatively smooth surface but without madarosis. The histopathological findings corresponded to a myeloid sarcoma. No blast cells were shown in the peripheral blood at the time of biopsy, and she subsequently underwent an azacitidine injection regimen. The size of the eyelid tumor decreased 3 months after the biopsy, when the course of azacitidine injections was completed. However, acute myeloid leukemia recurred, and the patient died PMID:26889156

  19. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

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

  20. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-08

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  1. The allometry of chronic myeloid leukemia.

    PubMed

    Pacheco, Jorge M; Traulsen, Arne; Dingli, David

    2009-08-01

    Chronic myeloid leukemia (CML) is an acquired neoplastic hematopoietic stem cell (HSC) disorder characterized by the expression of the BCR-ABL oncoprotein. This gene product is necessary and sufficient to explain the chronic phase of CML. The only known cause of CML is radiation exposure leading to a mutation of at least one HSC, although the vast majority of patients with CML do not have a history of radiation exposure. Nonetheless, in humans, significant radiation exposure (after exposure to atomic bomb fallout) leads to disease diagnosis in 3-5 years. In murine models, disease dynamics are much faster and CML is fatal over the span of a few months. Our objective is to develop a model that accounts for CML across all mammals. In the following, we combine a model of CML dynamics in humans with allometric scaling of hematopoiesis across mammals to illustrate the natural history of chronic phase CML in various mammals. We show how a single cell can lead to a fatal illness in mice and humans but a higher burden of CML stem cells is necessary to induce disease in larger mammals such as elephants. The different dynamics of the disease is rationalized in terms of mammalian mass. Our work illustrates the relevance of animal models to understand human disease and highlights the importance of considering the re-scaling of the dynamics that accrues to the same biological process when planning experiments involving different species. PMID:19362566

  2. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia.

    PubMed

    Nanjappa, Sowmya; Jeong, Daniel K; Muddaraju, Manjunath; Jeong, Katherine; Hill, Ebone D; Greene, John N

    2016-07-01

    Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed. PMID:27556667

  3. An HSEF for murine myeloid leukemia

    SciTech Connect

    Bond, V.P.; Cronkite, E.P.; Bullis, J.E.; Wuu, C.S.; Marino, S.A.; Zaider, M.

    1996-10-01

    In the past decade, a large amount of effort has gone into the development of hit size effectiveness functions (HSEFs), with the ultimate aim of replacing the present absorbed dose-RBE-Q system. However, the absorbed dose determined at the tissue level is incapable of providing information on single hits on (doses to) the single cell. As a result, it is necessary to resort to microdosimetry, which is capable of providing not only the number of hits on cells, but the distribution of hit sizes as well. From this information, an HSEF can be derived. However, to date there have been no sets of data available on animals exposed to radiations of several qualities, and for which microdosimetric data were available. The objective of the present set of experiments was to remedy this situation. Large numbers of mice were exposed to radiations of several different qualities, and were observed throughout their entire lifespan for the appearance of myeloid leukemia. The HSEF developed for this neoplasm is presented and discussed.

  4. Genome Wide Mapping of NR4A Binding Reveals Cooperativity with ETS Factors to Promote Epigenetic Activation of Distal Enhancers in Acute Myeloid Leukemia Cells

    PubMed Central

    Duren, Ryan P.; Boudreaux, Seth P.; Conneely, Orla M.

    2016-01-01

    Members of the NR4A subfamily of orphan nuclear receptors regulate cell fate decisions via both genomic and non-genomic mechanisms in a cell and tissue selective manner. NR4As play a key role in maintenance of hematopoietic stem cell homeostasis and are critical tumor suppressors of acute myeloid leukemia (AML). Expression of NR4As is broadly silenced in leukemia initiating cell enriched populations from human patients relative to normal hematopoietic stem/progenitor cells. Rescue of NR4A expression in human AML cells inhibits proliferation and reprograms AML gene signatures via transcriptional mechanisms that remain to be elucidated. By intersecting an acutely regulated NR4A1 dependent transcriptional profile with genome wide NR4A binding distribution, we now identify an NR4A targetome of 685 genes that are directly regulated by NR4A1. We show that NR4As regulate gene transcription primarily through interaction with distal enhancers that are co-enriched for NR4A1 and ETS transcription factor motifs. Using a subset of NR4A activated genes, we demonstrate that the ETS factors ERG and FLI-1 are required for activation of NR4A bound enhancers and NR4A target gene induction. NR4A1 dependent recruitment of ERG and FLI-1 promotes binding of p300 histone acetyltransferase to epigenetically activate NR4A bound enhancers via acetylation at histone H3K27. These findings disclose novel epigenetic mechanisms by which NR4As and ETS factors cooperate to drive NR4A dependent gene transcription in human AML cells. PMID:26938745

  5. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

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

    ClinicalTrials.gov

    2016-08-10

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

  7. MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-25

    Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  8. Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-08-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Myelodysplastic Syndrome; Childhood Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

  9. Effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells and leukemia mice

    PubMed Central

    Jia, Xinyan; Yang, Wenzhong; Han, Jia; Xiong, Hong

    2014-01-01

    Objective: To investigate the effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells (K562) and the growth of chronic myeloid leukemia mice as well as to explore the potential mechanisms. Methods: Unbtreated K562 cells (CON), blank lentivirus transfected K562 cells (NC) and K562 cells expressing STAT3 siRNA (STAT3 siRNA) were injected into SCID mice to establish the chronic myeloid leukemia model in mice. The growth, peripheral white blood cell count and spleen index in these mice were determined. Results: In vitro experiment showed, when compared with control group, the interference efficiency of STAT3 expression was as high as 97.5% in K562 cells. Western blot assay revealed that the expression of c-Myc, Bcl-xL and Cyclin D1 reduced by 17.01%, 7.3% and 6.82%, respectively, showing significant difference when compared with control group (P < 0.01). These findings were consistent with those from fluorescence quantitative PCR. In vivo experiment showed the body weight of mice reduced progressively and the peripheral white blood cell count increased gradually in control group, accompanied by dragging hind limbs and progressive enlargement of the spleen. The body weight remained unchanged, peripheral white blood cell count reduced gradually and the spleen did not enlarge in mice treated with STAT3 siRNA expressing cells. Conclusion: Lentivirus mediated STAT3 silencing may inhibit the expression of its downstream genes (c-Myc, Bcl-xL and Cyclin D1) related to cell proliferation, apoptosis and cycle to suppress the malignant biological behaviors, and STAT3 silencing also inhibit the leukemogenic potency of K562 cells in mice. PMID:25550912

  10. Diagnosing and managing advanced chronic myeloid leukemia.

    PubMed

    Deininger, Michael W

    2015-01-01

    Clinical staging of chronic myeloid leukemia (CML) distinguishes between chronic phase (CP-CML), accelerated phase (AP-CML), and blastic phase (BP-CML), reflecting its natural history in the absence of effective therapy. Morphologically, transformation from CP-CML to AP/BP-CML is characterized by a progressive or sudden loss of differentiation. Multiple different somatic mutations have been implicated in transformation from CP-CML to AP/BC-CML, but no characteristic mutation or combination of mutations have emerged. Gene expression profiles of AP-CML and BP-CML are similar, consistent with biphasic evolution at the molecular level. Gene expression of tyrosine kinase inhibitor (TKI)-resistant CP-CML and second CP-CML resemble AP/BP-CML, suggesting that morphology alone is a poor predictor of biologic behavior. At the clinical level, progression to AP/BP-CML or resistance to first-line TKI therapy distinguishes a good risk condition with survival close to the general population from a disease likely to reduce survival. Progression while receiving TKI therapy is frequently caused by mutations in the target kinase BCR-ABL1, but progression may occur in the absence of explanatory BCR-ABL1 mutations, suggesting involvement of alternative pathways. Identifying patients in whom milestones of TKI response fail to occur or whose disease progress while receiving therapy requires appropriate molecular monitoring. Selection of salvage TKI depends on prior TKI history, comorbidities, and BCR-ABL1 mutation status. Despite the introduction of novel TKIs, therapy of AP/BP-CML remains challenging and requires accepting modalities with substantial toxicity, such as hematopoietic stem cell transplantation (HSCT). PMID:25993200

  11. Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

    SciTech Connect

    Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion; E-mail: bkatz@tasmc.healt.gov.il

    2005-10-07

    Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RAR{alpha} and PLZF-RAR{alpha} fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RAR{alpha} from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells.

  12. Splenic actinomycotic abscess in a patient with acute myeloid leukemia.

    PubMed

    Chen, C-Y; Chen, Y-C; Tang, J-L; Lin, W-C; Su, I-J; Tien, H-F

    2002-09-01

    Actinomycosis is a gram-positive anaerobic bacterium. Actinomyces organisms are important constituents of the normal flora of mucous membranes and are considered opportunistic pathogens. The three major clinical presentations of actinomycosis include the cervicofacial, thoracic, and abdominopelvic regions. Actinomycosis infection in patients with febrile neutropenia is uncommon and actinomycosis splenic involvement in acute leukemia patients is very rare. We describe a man with acute myeloid leukemia and splenic actinomycotic abscess that developed after chemotherapy following prolonged neutropenia. PMID:12373356

  13. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

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

  14. Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.

    PubMed

    Gambacorti-Passerini, Carlo B; Donadoni, Carla; Parmiani, Andrea; Pirola, Alessandra; Redaelli, Sara; Signore, Giovanni; Piazza, Vincenzo; Malcovati, Luca; Fontana, Diletta; Spinelli, Roberta; Magistroni, Vera; Gaipa, Giuseppe; Peronaci, Marco; Morotti, Alessandro; Panuzzo, Cristina; Saglio, Giuseppe; Usala, Emilio; Kim, Dong-Wook; Rea, Delphine; Zervakis, Konstantinos; Viniou, Nora; Symeonidis, Argiris; Becker, Heiko; Boultwood, Jacqueline; Campiotti, Leonardo; Carrabba, Matteo; Elli, Elena; Bignell, Graham R; Papaemmanuil, Elli; Campbell, Peter J; Cazzola, Mario; Piazza, Rocco

    2015-01-15

    Despite the recent identification of recurrent SETBP1 mutations in atypical chronic myeloid leukemia (aCML), a complete description of the somatic lesions responsible for the onset of this disorder is still lacking. To find additional somatic abnormalities in aCML, we performed whole-exome sequencing on 15 aCML cases. In 2 cases (13.3%), we identified somatic missense mutations in the ETNK1 gene. Targeted resequencing on 515 hematological clonal disorders revealed the presence of ETNK1 variants in 6 (8.8%) of 68 aCML and 2 (2.6%) of 77 chronic myelomonocytic leukemia samples. These mutations clustered in a small region of the kinase domain, encoding for H243Y and N244S (1/8 H243Y; 7/8 N244S). They were all heterozygous and present in the dominant clone. The intracellular phosphoethanolamine/phosphocholine ratio was, on average, 5.2-fold lower in ETNK1-mutated samples (P < .05). Similar results were obtained using myeloid TF1 cells transduced with ETNK1 wild type, ETNK1-N244S, and ETNK1-H243Y, where the intracellular phosphoethanolamine/phosphocholine ratio was significantly lower in ETNK1-N244S (0.76 ± 0.07) and ETNK1-H243Y (0.37 ± 0.02) than in ETNK1-WT (1.37 ± 0.32; P = .01 and P = .0008, respectively), suggesting that ETNK1 mutations may inhibit the catalytic activity of the enzyme. In summary, our study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders. PMID:25343957

  15. Acute Myeloid Leukemia Presenting as Intracerebral Granulocytic Sarcoma.

    PubMed

    Dhandapani, E; Thirumavalavan; Sowrirajan

    2015-10-01

    The CNS involvement of acute myeloid leukemia (AML) is more commonly manifest as meningeal involvement. Rarely it may present as intravascular tumor aggregates called granulocytic sarcoma which presents as intracranial hemorrhage. We are presenting a case of intracranial, intra-parenchymal granulocytic sarcoma (other names: chloroma, extramedullary myeloblastoma), presenting as acute hemiplegia without cerebral hemorrhage. PMID:27608697

  16. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia

    PubMed Central

    Ye, Qi; Jiang, Jue; Zhan, Guanqun; Yan, Wanyao; Huang, Liang; Hu, Yufeng; Su, Hexiu; Tong, Qingyi; Yue, Ming; Li, Hua; Yao, Guangmin; Zhang, Yonghui; Liu, Hudan

    2016-01-01

    Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML. PMID:27211848

  17. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia.

    PubMed

    Ye, Qi; Jiang, Jue; Zhan, Guanqun; Yan, Wanyao; Huang, Liang; Hu, Yufeng; Su, Hexiu; Tong, Qingyi; Yue, Ming; Li, Hua; Yao, Guangmin; Zhang, Yonghui; Liu, Hudan

    2016-01-01

    Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML. PMID:27211848

  18. A novel karyotype in acute myeloid leukemia with basophilia.

    PubMed

    Servitzoglou, Marina; Grenzelia, Maria; Baka, Margarita; Harisi, Marietta; Pourtsidis, Apostolos; Bouhoutsou, Despina; Varvoutsi, Maria; Doganis, Dimitrios; Dana, Helen; Divane, Aspasia; Kosmidis, Helen

    2014-03-01

    Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, -21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity. PMID:24552500

  19. Cauda equina involvement in acute myeloid leukemia relapse.

    PubMed

    Buakhao, Jitsuda; Tansawet, Amarate

    2011-10-01

    Although central nervous system (CNS) involvement in acute myeloid leukemia has been described in about 2 to 4%, it still represents a major therapeutic problem, particularly cauda eqina involvement that is clinically significant and unusual. Here, a 22-year-old man, with underlying AML (M2-Subtype, FAB classification) and cytogenetic analysis resulted in 45, x, -y, t(8;21) (q22;q22)[15] whose presenting symptoms of low back pain and incontinence, 10 months after first remission, was reported. This was followed by peripheral and bone marrow relapse. The magnetic resonance image (MRI) findings revealed leukemic infiltration at S1-S5 of the spinal cord canal with associated soft tissue component at presacral area encasing bilateral S1-S5 exiting root with heterogeneous enhancement in bone marrow of S2-S4. The therapeutic and prognosis implications of spinal cord involvement by leukemia were discussed. Because of severe morbidity, the patient developed bone marrow failure and died from sepsis. PMID:22145515

  20. MTHFR gene polymorphism and risk of myeloid leukemia: a meta-analysis.

    PubMed

    Dong, Song; Liu, Yueling; Chen, Jieping

    2014-09-01

    An increasing body of evidence has shown that the amino acid changes at position 1298 might eliminate methylenetetrahydrofolate reductase (MTHFR) enzyme activity, leading to insufficient folic acid and subsequent human chromosome breakage. Epidemiological studies have linked MTHFR single-nucleotide polymorphism (SNP) rs1801131 to myeloid leukemia risk, with considerable discrepancy in their results. We therefore were prompted to clarify this issue by use of a meta-analysis. The search terms were used to cover the possible reports in the MEDLINE, Web of Knowledge, and China National Knowledge Infrastructure (CNKI) databases. Odds ratios were estimated to assess the association of SNP rs1801131 with myeloid leukemia risk. Statistical heterogeneity was detected using the Q-statistic and I (2) metric. Subgroup analysis was performed by ethnicity, histological subtype, and Hardy-Weinberg equilibrium (HWE). This meta-analysis of eight publications with a total of 1,114 cases and 3,227 controls revealed no global association. Nor did the subgroup analysis according to histological subtype and HWE show any significant associations. However, Asian individuals who harbored the CC genotype were found to have 1.66-fold higher risk of myeloid leukemia (odds ratio, 1.66; 95 % confidence interval, 1.10 to 2.49; P h = 0.342; I (2) = 0.114). Our meta-analysis has presented evidence supporting a possible association between the CC genotype of MTHFR SNP rs1801131 and myeloid leukemia in Asian populations. PMID:24894669

  1. Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  2. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2013-06-03

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

  4. BCL11A expression in acute phase chronic myeloid leukemia.

    PubMed

    Yin, Jiawei; Zhang, Fan; Tao, Huiquan; Ma, Xiao; Su, Guangsong; Xie, Xiaoli; Xu, Zhongjuan; Zheng, Yanwen; Liu, Hong; He, Chao; Mao, Zhengwei Jenny; Wang, Zhiwei; Chang, Weirong; Gale, Robert Peter; Wu, Depei; Yin, Bin

    2016-08-01

    Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons. PMID:27285855

  5. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-10-09

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  6. cDNA cloning, tissue distribution, and chromosomal localization of myelodysplasia/Myeloid Leukemia Factor 2 (MLF2)

    SciTech Connect

    Kuefer, M.U.; Valentine, V.; Behm, F.G.

    1996-07-15

    A fusion gene between nucleophosmin (NPM) and myelodysplasia/myeloid leukemia factor 1 (MLF1) and myelodysplasia/myeloid leukemia factor 1 (MLF1) is formed by a recurrent t(3;5)(q25.1;q34) in myelodysplastic syndrome and acute myeloid leukemia. Here we report the identification of a novel gene, MLF2, which contains an open reading frame of 744 bp encoding a 248-amino-acid protein highly related to the previously identified MLF1 protein (63% similarity, 40% identity). In contrast to the tissue-restricted expression pattern of MLF1, and MLF2 messenger RNA is expressed ubiquitously. The MLF2 gene locus was mapped by fluorescence in situ hybridization to human chromosome 12p13, a chromosomal region frequently involved in translocations and deletions in acute leukemias of lymphoid or myeloid lineage. In a physical map of chromosome 12, MLF2 was found to reside on the yeast artificial chromosome clone 765b9. Southern blotting analysis of malignant cell DNAs prepared from a series of acute lymphoblastic leukemia cases with translocations involving chromosome arm 12p, as well as a group of acute myeloid leukemias with various cytogenetic abnormalities, failed to reveal MLF2 gene rearrangements. 19 refs., 2 figs.

  7. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-16

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

  8. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2016-01-19

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

  9. Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

    ClinicalTrials.gov

    2013-08-06

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  10. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  11. Monitoring imatinib plasma concentrations in chronic myeloid leukemia

    PubMed Central

    Martins, Darlize Hübner; Wagner, Sandrine Comparsi; dos Santos, Tamyris Vianna; Lizot, Lilian de Lima Feltraco; Antunes, Marina Venzon; Capra, Marcelo; Linden, Rafael

    2011-01-01

    Imatinib has proved to be effective in the treatment of chronic myeloid leukemia, but plasma levels above 1,000 ng/mL must be achieved to optimize activity. Therapeutic drug monitoring of imatinib is useful for patients that do not present clinical response. There are several analytical methods to measure imatinib in biosamples, which are mainly based on liquid chromatography with mass spectrometric or diode array spectrophotometric detection. The former is preferred due to its lower cost and wider availability. The present manuscript presents a review of the clinical and analytical aspects of the therapeutic drug monitoring of imatinib in the treatment of chronic myeloid leukemia. The review includes references published over the last 10 years. There is evidence that the monitoring of plasmatic levels of imatinib is an useful alternative, especially considering the wide pharmacokinetic variability of this drug. PMID:23049322

  12. 'Acute myeloid leukemia: a comprehensive review and 2016 update'.

    PubMed

    De Kouchkovsky, I; Abdul-Hay, M

    2016-01-01

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with an incidence of over 20 000 cases per year in the United States alone. Large chromosomal translocations as well as mutations in the genes involved in hematopoietic proliferation and differentiation result in the accumulation of poorly differentiated myeloid cells. AML is a highly heterogeneous disease; although cases can be stratified into favorable, intermediate and adverse-risk groups based on their cytogenetic profile, prognosis within these categories varies widely. The identification of recurrent genetic mutations, such as FLT3-ITD, NMP1 and CEBPA, has helped refine individual prognosis and guide management. Despite advances in supportive care, the backbone of therapy remains a combination of cytarabine- and anthracycline-based regimens with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens, and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of AML. PMID:27367478

  13. Acute pediatric leg compartment syndrome in chronic myeloid leukemia.

    PubMed

    Cohen, Eric; Truntzer, Jeremy; Trunzter, Jeremy; Klinge, Steve; Schwartz, Kevin; Schiller, Jonathan

    2014-11-01

    Acute compartment syndrome is an orthopedic surgical emergency and may result in devastating complications in the setting of delayed or missed diagnosis. Compartment syndrome has a variety of causes, including posttraumatic or postoperative swelling, external compression, burns, bleeding disorders, and ischemia-reperfusion injury. Rare cases of pediatric acute compartment syndrome in the setting of acute myeloid leukemia and, even less commonly, chronic myeloid leukemia have been reported. The authors report the first known case of pediatric acute compartment syndrome in a patient without a previously known diagnosis of chronic myeloid leukemia. On initial examination, an 11-year-old boy presented with a 2-week history of progressive left calf pain and swelling after playing soccer. Magnetic resonance imaging scan showed a hematoma in the left superficial posterior compartment. The patient had unrelenting pain, intermittent lateral foot parethesias, and inability to bear weight. Subsequently, he was diagnosed with acute compartment syndrome and underwent fasciotomy and evacuation of a hematoma. Laboratory results showed an abnormal white blood cell count of 440×10(9)/L (normal, 4.4-11×10(9)) and international normalized ratio of 1.3 (normal, 0.8-1.2). Further testing included the BCR-ABL1 fusion gene located on the Philadelphia chromosome, leading to a diagnosis of chronic myeloid leukemia. Monotherapy with imatinib mesylate (Gleevec) was initiated. This report adds another unique case to the growing literature on compartment syndrome in the pediatric population and reinforces the need to consider compartment syndrome, even in unlikely clinical scenarios. PMID:25361367

  14. MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Acute Myeloid Leukemia: Biologic, Prognostic, and Therapeutic Insights.

    PubMed

    Khaled, Samer; Al Malki, Monzr; Marcucci, Guido

    2016-04-01

    Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Unfortunately, currently used "one-size-fits-all" chemotherapy regimens result in cure for only a minority of patients. Although progress has been made in identifying subsets of patients who require chemotherapy alone-as compared with those who require initial chemotherapy followed by allogeneic stem cell transplantation to maximize the chance for cure-clinical and cytogenetic prognosticators are not sufficiently accurate for such a risk-adapted stratification approach. New molecular technologies have allowed for in-depth molecular analyses of AML patients. These studies have revealed novel mutations, epigenetic changes, and/or aberrant expression levels of protein-coding and noncoding genes involved in leukemogenesis. These molecular aberrations are now being increasingly used not only to select risk-adapted treatment strategies, but also to incorporate newer molecularly targeted agents into conventional chemotherapy and/or transplant treatments. The hope is that this approach will lead to a better selection of "personalized" treatments for individual patients at diagnosis, the ability to assess these treatments in real time, and the ability, if necessary, to modify these therapies utilizing molecular endpoints for guidance regarding their antileukemia activity. We review here the state of the art of diagnosis and treatment of AML and provide insights into the emerging novel biomarkers and therapeutic agents that are anticipated to be useful for the implementation of personalized medicine in AML. PMID:27085330

  16. Acute myeloid leukemia in children: Current status and future directions.

    PubMed

    Taga, Takashi; Tomizawa, Daisuke; Takahashi, Hiroyuki; Adachi, Souichi

    2016-02-01

    Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML-DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all-trans retinoic acid (ATRA)-combined regimen with an 80-90% OS. Children with ML-DS are treated with a less intensive regimen compared with non-DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high-risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials. PMID:26645706

  17. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis.

    PubMed

    Kolenova, Alexandra; Maloney, Kelly W; Hunger, Stephen P

    2016-08-01

    The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC. PMID:27164534

  18. STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia.

    PubMed

    Curran, Emily; Chen, Xiufen; Corrales, Leticia; Kline, Douglas E; Dubensky, Thomas W; Duttagupta, Priyanka; Kortylewski, Marcin; Kline, Justin

    2016-06-14

    Type I interferon (IFN), essential for spontaneous T cell priming against solid tumors, is generated through recognition of tumor DNA by STING. Interestingly, we observe that type I IFN is not elicited in animals with disseminated acute myeloid leukemia (AML). Further, survival of leukemia-bearing animals is not diminished in the absence of type I IFN signaling, suggesting that STING may not be triggered by AML. However, the STING agonist, DMXAA, induces expression of IFN-β and other inflammatory cytokines, promotes dendritic cell (DC) maturation, and results in the striking expansion of leukemia-specific T cells. Systemic DMXAA administration significantly extends survival in two AML models. The therapeutic effect of DMXAA is only partially dependent on host type I IFN signaling, suggesting that other cytokines are important. A synthetic cyclic dinucleotide that also activates human STING provided a similar anti-leukemic effect. These data demonstrate that STING is a promising immunotherapeutic target in AML. PMID:27264175

  19. Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death.

    PubMed

    Feng, Qian; Leong, Wa Seng; Liu, Liang; Chan, Wai-In

    2016-01-01

    Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34⁺CD38(-) leukemic stem-like cells, but not the more mature CD34⁺CD38⁺ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G₂/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future. PMID:27110755

  20. Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-03-30

    Acute Leukemia of Ambiguous Lineage; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

    ClinicalTrials.gov

    2015-12-28

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

  2. Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-03-01

    Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

  3. Advances in immunotherapy of chronic myeloid leukemia CML.

    PubMed

    Held, Stefanie Andrea Erika; Heine, Annkristin; Mayer, Karin Tina; Kapelle, Mario; Wolf, Dominik Georg Friedrich; Brossart, Peter

    2013-09-01

    Tyrosine kinase inhibitors induce sustained disease remissions in chronic myeloid leukemia by exploiting the addiction of this type of leukemia to the activity of the fusion oncogene BCR-ABL. However, these agents fail to eradicate CML stem cells which are ultimately responsible for disease relapses upon treatment discontinuation. Evidence that the immune system can effectively reject CML stem cells potentially leading to patient cure is provided by the experience with patients receiving allogeneic bone marrow transplantations. Compelling evidence indicates that more modern, antigen-specific immunotherapeutic approaches are also feasible and hold strong potential to be clinically effective. Amongst these, particularly promising is the use of autologous dendritic cells pulsed with antigens or direct application of in vitro transcribed RNA encoding for leukemia-associated antigens, since this approach allows to circumvent HLA-restriction of the leukemia-associated T cell epitopes that have been eventually identified. Combining these strategies with monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1, may help to obtain even stronger immune responses and better clinical results. This narrative review addresses this topic by focusing in particular on the cell-based immunotherapeutic strategies for CML and on the issue of the leukemia-associated antigens to be selected for targeting. PMID:23906051

  4. Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia

    PubMed Central

    Mosna, Federico

    2016-01-01

    Even though clonally originated from a single cell, acute leukemia loses its homogeneity soon and presents at clinical diagnosis as a hierarchy of cells endowed with different functions, of which only a minority possesses the ability to recapitulate the disease. Due to their analogy to hematopoietic stem cells, these cells have been named “leukemia stem cells,” and are thought to be chiefly responsible for disease relapse and ultimate survival after chemotherapy. Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) is cytogenetically characterized by either the t(8;21) or the inv(16)/t(16;16) chromosomal abnormalities, which, although being pathognomonic, are not sufficient per se to induce overt leukemia but rather determine a preclinical phase of disease when preleukemic subclones compete until the acquisition of clonal dominance by one of them. In this review we summarize the concepts regarding the application of the “leukemia stem cell” theory to the development of CBF AML; we will analyze the studies investigating the leukemogenetic role of t(8;21) and inv(16)/t(16;16), the proposed theories of its clonal evolution, and the role played by the hematopoietic niches in preserving the disease. Finally, we will discuss the clinical implications of stem cell modeling of CBF AML for the therapy of the disease. PMID:26880987

  5. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.

    PubMed

    Zwaan, C Michel; Kolb, Edward A; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S J M; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E S; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C; Rizzari, Carmelo; Rubnitz, Jeffrey E; Smith, Owen P; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M; Creutzig, Ursula; Kaspers, Gertjan J L

    2015-09-20

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. PMID:26304895

  6. Chronic Myeloid Leukemia--Prognostic Value of Mutations.

    PubMed

    Kaleem, Bushra; Shahab, Sadaf; Ahmed, Nuzhat; Shamsi, Tahir Sultan

    2015-01-01

    Chronic myeloid leukemia (CML) is a stem cell disorder characterized by unrestricted proliferation of the myeloid series that occurs due to the BCR-ABL fusion oncogene as a result of reciprocal translocation t(9;22) (q34;q11). This discovery has made this particular domain a target for future efforts to cure CML. Imatinib revolutionized the treatment options for CML and gave encouraging results both in case of safety as well as tolerability profile as compared to agents such as hydroxyurea or busulfan given before Imatinib. However, about 2-4% of patients show resistance and mutations have been found to be one of the reasons for its development. European Leukemianet gives recommendations for BCR-ABL mutational analysis along with other tyrosine kinase inhibitors (TKIs) that should be administered according to the mutations harbored in a patient. The following overview gives recommendations for monitoring patients on the basis of their mutational status. PMID:26625737

  7. 2-D gel electrophoresis-based proteomic analysis reveals that ormeloxifen induces G0-G1 growth arrest and ERK-mediated apoptosis in chronic myeloid leukemia cells K562.

    PubMed

    Pal, Pooja; Kanaujiya, Jitendra K; Lochab, Savita; Tripathi, Shashi B; Bhatt, Madan L B; Singh, Pradhyumna K; Sanyal, Sabyasachi; Trivedi, Arun K

    2011-04-01

    Ormeloxifen is a nonsteroidal selective estrogen receptor modulator (SERM) and has been shown to possess anticancer activities in breast and uterine cancer. Here, we show that ormeloxifen induces apoptosis in dose-dependent manner in a variety of leukemia cells, more strikingly in K562. 2-DE-gel electrophoresis of K562 cells induced with ormeloxifen showed that 57 and 30% of proteins belong to apoptosis and cell-cycle pathways, respectively. Our data demonstrate that ormeloxifen-induced apoptosis in K562 cells involves activation of extracellular signal-regulated kinases (ERKs) and subsequent cytochrome c release, leading to mitochondria-mediated caspase-3 activation. Ormeloxifen-induced apoptosis via ERK activation was drastically inhibited by prior treatment of K562 cells with ERK inhibitor PD98059. Ormeloxifen also inhibits proliferation of K562 cells by blocking them in G0-G1 phase by inhibiting c-myc promoter via ormeloxifen-induced MBP-1 (c-myc promoter-binding protein) and upregulation of p21 expression. We further show that ormeloxifen-induced apoptosis in K562 is translatable to mononuclear cells isolated from chronic myeloid leukemia (CML) patients. Thus, ormeloxifen induces apoptosis in K562 cells via phosphorylation of ERK and arrests them in G0-G1 phase by reciprocal regulation of p21 and c-myc. Therefore, inclusion of ormeloxifen in the therapy of chronic myeloid leukemia can be of potential utility. PMID:21360677

  8. Comprehensive mutational profiling of core binding factor acute myeloid leukemia.

    PubMed

    Duployez, Nicolas; Marceau-Renaut, Alice; Boissel, Nicolas; Petit, Arnaud; Bucci, Maxime; Geffroy, Sandrine; Lapillonne, Hélène; Renneville, Aline; Ragu, Christine; Figeac, Martin; Celli-Lebras, Karine; Lacombe, Catherine; Micol, Jean-Baptiste; Abdel-Wahab, Omar; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

    2016-05-19

    Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been recognized as unique entities within AML and are usually reported together as core binding factor AML (CBF-AML). However, there is considerable clinical and biological heterogeneity within this group of diseases, and relapse incidence reaches up to 40%. Moreover, translocations involving CBFs are not sufficient to induce AML on its own and the full spectrum of mutations coexisting with CBF translocations has not been elucidated. To address these issues, we performed extensive mutational analysis by high-throughput sequencing in 215 patients with CBF-AML enrolled in the Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor Acute Myeloid Leukemia and Treating Patients with Childhood Acute Myeloid Leukemia with Interleukin-2 trials (age, 1-60 years). Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML. PMID:26980726

  9. BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia.

    PubMed

    Roe, Jae-Seok; Mercan, Fatih; Rivera, Keith; Pappin, Darryl J; Vakoc, Christopher R

    2015-06-18

    The bromodomain and extraterminal (BET) protein BRD4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that BRD4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) PU.1, FLI1, ERG, C/EBPα, C/EBPβ, and MYB at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate BRD4 recruitment to their occupied sites to promote transcriptional activation. Chemical inhibition of BET bromodomains was found to suppress the functional output of each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and BRD4 that supports leukemia maintenance and is suppressed by BET bromodomain inhibition. PMID:25982114

  10. Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia.

    PubMed

    Cheung, Ngai; Fung, Tsz Kan; Zeisig, Bernd B; Holmes, Katie; Rane, Jayant K; Mowen, Kerri A; Finn, Michael G; Lenhard, Boris; Chan, Li Chong; So, Chi Wai Eric

    2016-01-11

    Transcriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming. Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant epigenetic circuitry mediated by KDM4C and PRMT1 in acute leukemia. PMID:26766589

  11. Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia

    PubMed Central

    Cheung, Ngai; Fung, Tsz Kan; Zeisig, Bernd B.; Holmes, Katie; Rane, Jayant K.; Mowen, Kerri A.; Finn, Michael G.; Lenhard, Boris; Chan, Li Chong; So, Chi Wai Eric

    2016-01-01

    Summary Transcriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming. Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant epigenetic circuitry mediated by KDM4C and PRMT1 in acute leukemia. PMID:26766589

  12. Acute Myeloid Leukemia Complicated by Giant Cell Arteritis.

    PubMed

    Tsunemine, Hiroko; Umeda, Ryosuke; Nohda, Yasuhiro; Sakane, Emiko; Akasaka, Hiroshi; Itoh, Kiminari; Izumi, Mayuko; Tsuji, Goh; Kodaka, Taiichi; Itoh, Tomoo; Takahashi, Takayuki

    2016-01-01

    Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin. PMID:26831026

  13. [Progress in molecularly targeted therapies for acute myeloid leukemia].

    PubMed

    Tomita, Akihiro

    2015-02-01

    Genetic abnormalities including specific point mutations have recently been confirmed by applying comprehensive genome sequencing analyses. Molecular targeting therapies, which focus on the mutated proteins and over-expressed proteins in acute myeloid leukemia (AML) cells, are now being developed in clinical studies and/or based on in vitro analyses. This manuscript summarizes the genetic abnormalities in AML cells and some of the current molecular targeting therapies including FLT3 inhibitors (e.g. AC220; Quizartinib), Polo like kinase 1 (PLK1) inhibitors (e.g. BI-6727; Volasertib), IDH2 inhibitors (e.g. AG-221), and XPO1 inhibitors (e.g. KPT-330; Selinexor). PMID:25765792

  14. Management of Acute Myeloid Leukemia in the Intensive Care Setting.

    PubMed

    Cowan, Andrew J; Altemeier, William A; Johnston, Christine; Gernsheimer, Terry; Becker, Pamela S

    2015-10-01

    Patients with acute myeloid leukemia (AML) who are newly diagnosed or relapsed and those who are receiving cytotoxic chemotherapy are predisposed to conditions such as sepsis due to bacterial and fungal infections, coagulopathies, hemorrhage, metabolic abnormalities, and respiratory and renal failure. These conditions are common reasons for patients with AML to be managed in the intensive care unit (ICU). For patients with AML in the ICU, providers need to be aware of common problems and how to manage them. Understanding the pathophysiology of complications and the recent advances in risk stratification as well as newer therapy for AML are relevant to the critical care provider. PMID:24756309

  15. Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

    ClinicalTrials.gov

    2016-06-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2013-01-09

    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

  17. ACER3 supports development of acute myeloid leukemia.

    PubMed

    Chen, Chen; Yin, Yancun; Li, Chunling; Chen, Jinliang; Xie, Jingjing; Lu, Zhigang; Li, Minjing; Wang, Yuesi; Zhang, Cheng Cheng

    2016-09-01

    No new therapy for acute myeloid leukemia (AML) has been approved for more than 30 years. To effectively treat AML, new molecular targets and therapeutic approaches must be identified. In silico analysis of several databases of AML patients demonstrated that the expression of alkaline ceramidase 3 (ACER3) significantly inversely correlates with the overall survival of AML patients. To determine whether ACER3 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit acer3 expression in human AML cells including NB4, U937, and THP-1 cells. The ACER3 deficiency resulted in decreased cell growth and colony formation, elevated apoptosis, and lower AKT signaling of leukemia cells. Our study indicates that ACER3 contributes to AML pathogenesis, and suggests that alkaline ceramidase inhibition is an option to treat AML. PMID:27470583

  18. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia

    PubMed Central

    Klco, Jeffery M.; Spencer, David H.; Miller, Christopher A.; Griffith, Malachi; Lamprecht, Tamara L.; O’Laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan T.; Fulton, Robert S.; Eades, William C.; Link, Daniel C.; Graubert, Timothy A.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Wilson, Richard K.; Ley, Timothy J.

    2014-01-01

    Summary The relationships between clonal architecture and functional heterogeneity in acute myeloid leukemia (AML) samples are not yet clear. We used targeted sequencing to track AML subclones identified by whole genome sequencing using a variety of experimental approaches. We found that virtually all AML subclones trafficked from the marrow to the peripheral blood, but some were enriched in specific cell populations. Subclones showed variable engraftment potential in immunodeficient mice. Xenografts were predominantly comprised of a single genetically-defined subclone, but there was no predictable relationship between the engrafting subclone and the evolutionary hierarchy of the leukemia. These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients. PMID:24613412

  19. Pharmacogenetics of alkylator-associated acute myeloid leukemia.

    PubMed

    Knoche, Eric; McLeod, Howard L; Graubert, Timothy A

    2006-07-01

    Therapy-related acute myeloid leukemia (t-AML) is a lethal late complication of alkylator chemotherapy. The genetic basis of susceptibility to t-AML is poorly understood. Both t-AML and de novo AML are complex genetic diseases, requiring cooperating mutations in interacting pathways for disease initiation and progression. Germline variants of these 'leukemia pathway' genes may cooperate with somatic mutations to induce both de novo and therapy-related AML. Several cancer susceptibility syndromes have been identified that cause an inherited predisposition to de novo and t-AML. The genes responsible for these syndromes are also somatically mutated in sporadic AML. We reason that germline polymorphism in any gene somatically mutated in AML could contribute to t-AML risk in the general population. Identification of these susceptibility alleles should help clinicians develop tailored therapies that reduce the relative risk of t-AML. PMID:16886897

  20. An overview of chronic myeloid leukemia and its animal models.

    PubMed

    Ma, WeiXu; Ma, Ning; Chen, XiaoHui; Zhang, YiYue; Zhang, WenQing

    2015-12-01

    Chronic myeloid leukemia (CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia (Ph) chromosome or t (9;22) translocation (BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors (TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish (Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML. PMID:26582013

  1. Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  2. Individual Telomere Lengths in Chronic Myeloid Leukemia12

    PubMed Central

    Samassekou, Oumar; Ntwari, Aimé; Hébert, Josée; Yan, Ju

    2009-01-01

    Chronic myeloid leukemia (CML) is a neoplasia characterized by proliferation of a myeloid cell lineage and chromosome translocation t(9;22) (q34;q11.2). As in the case of most cancers, the average telomere length in CML cells is shorter than that in normal blood cells. However, there are currently no data available concerning specific individual telomere length in CML. Here, we studied telomere length on each chromosome arm of CML cells. In situ hybridization with peptide nucleic acid probes was performed on CML cells in metaphase. The fluorescence intensity of each specific telomere was converted into kilobases according to the telomere restriction fragment results for each sample. We found differences in telomere length between short arm ends and long arm ends. We observed recurrent telomere length changes as well as telomere length maintenance and elongation in some individual telomeres. We propose a possible involvement of individual telomere length changes to some chromosomal abnormalities in CML. We suggest that individual telomere length maintenance is chromosome arm-specific associated with leukemia cells. PMID:19881950

  3. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  4. Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia

    PubMed Central

    Aue, Georg; Du, Yang; Cleveland, Susan M.; Smith, Stephen B.; Davé, Utpal P.; Liu, Delong; Weniger, Marc A.; Metais, Jean Yves; Jenkins, Nancy A.; Copeland, Neal G.

    2011-01-01

    Cooperation of multiple mutations is thought to be required for cancer development. In previous studies, murine myeloid leukemias induced by transducing wild-type bone marrow progenitors with a SRY sex determining region Y-box 4 (Sox4)–expressing retrovirus frequently carried proviral insertions at Sfpi1, decreasing its mRNA levels, suggesting that reduced Sfpi1 expression cooperates with Sox4 in myeloid leukemia induction. In support of this hypothesis, we show here that mice receiving Sox4 virus-infected Sfpi1ko/+ bone marrow progenitors developed myeloid leukemia with increased penetrance and shortened latency. Interestingly, Sox4 expression further decreased Sfpi1 transcription. Ectopic SOX4 expression reduced endogenous PU.1 mRNA levels in HL60 promyelocytes, and decreased Sfpi1 mRNA levels were also observed in the spleens of leukemic and preleukemic mice receiving Sox4 virus-infected wild-type bone marrow cells. In addition, Sox4 protein bound to a critical upstream regulatory element of Sfpi1 in ChIP assays. Such cooperation probably occurs in de novo human acute myeloid leukemias, as an analysis of 285 acute myeloid leukemia patient samples found a significant negative correlation between SOX4 and PU.1 expression. Our results establish a novel cooperation between Sox4 and reduced Sfpi1 expression in myeloid leukemia development and suggest that SOX4 could be an important new therapeutic target in human acute myeloid leukemia. PMID:21878674

  5. [Recent Advances of Research on CEBPA Mutation in Acute Myeloid Leukemia].

    PubMed

    Yu, Wen-Qing; Sun, Jing-Nan; Tan, Ye-Hui; Cui, Jiu-Wei; Li, Wei

    2015-12-01

    CCAAT/enhancer binding protein alpha gene (CEBPA) is an important transcription factor in maintenance of differentiation of granulocyte series of hematopoietic system. It plays a key role in regulating cell proliferation and differentiation. CEBPA mutation easily occurs in M1 and M2 type of acute myeloid leukemia, about 5%-14% in adult acute myeloid leukemia and 7.9% in children with acute myeloid leukemia. At present, domestic CEBPA mutation research is far less than abroad. This review focuses on the structual characteristics and detection method of CEBPA, CEBPA clinical features, the effect of CEBPA mutation on the prognosis of patients and the choice of treatment. PMID:26708912

  6. Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia

    PubMed Central

    Rampal, Raajit; Figueroa, Maria E.

    2016-01-01

    Wilms tumor 1 (WT1) has long been implicated in acute myeloid leukemia. It has been described to be both overexpressed and mutated in different forms of acute myeloid leukemia, and overexpression has been reported to play a prognostic role in this disease. However, the precise mechanism through which WT1 may play a role in leukemogenesis has remained elusive. In recent years, new evidence has emerged that points towards a novel role of WT1 mutations in the deregulation of epigenetic programs in leukemic cells through its interaction with TET proteins. Herein we review the current status of the field and its therapeutic and prognostic implications in acute myeloid leukemia. PMID:27252512

  7. Molecular dissection of valproic acid effects in acute myeloid leukemia identifies predictive networks.

    PubMed

    Rücker, Frank G; Lang, Katharina M; Fütterer, Markus; Komarica, Vladimir; Schmid, Mathias; Döhner, Hartmut; Schlenk, Richard F; Döhner, Konstanze; Knudsen, Steen; Bullinger, Lars

    2016-07-01

    Histone deacetylase inhibitors (HDACIs) like valproic acid (VPA) display activity in leukemia models and induce tumor-selective cytotoxicity against acute myeloid leukemia (AML) blasts. As there are limited data on HDACIs effects, we aimed to dissect VPA effects in vitro using myeloid cell lines with the idea to integrate findings with in vivo data from AML patients treated with VPA additionally to intensive chemotherapy (n = 12). By gene expression profiling we identified an in vitro VPA response signature enriched for genes/pathways known to be implicated in cell cycle arrest, apoptosis, and DNA repair. Following VPA treatment in vivo, gene expression changes in AML patients showed concordant results with the in vitro VPA response despite concomitant intensive chemotherapy. Comparative miRNA profiling revealed VPA-associated miRNA expression changes likely contributing to a VPA-induced reversion of deregulated gene expression. In addition, we were able to define markers predicting VPA response in vivo such as CXCR4 and LBH. These could be validated in an independent cohort of VPA and intensive chemotherapy treated AML patients (n = 114) in which they were inversely correlated with relapse-free survival. In summary, our data provide new insights into the molecular mechanisms of VPA in myeloid blasts, which might be useful in further advancing HDAC inhibition based treatment approaches in AML. PMID:27309669

  8. Diffuse leukoencephalopathy and brain edema: unusual presentations of CNS relapse of acute myeloid leukemia.

    PubMed

    Schumann, Michael; Kiewe, Philipp; Hartlieb, Sissel; Neumann, Martin; Schilling, Andreas; Koch, Hans-Christian; Thiel, Eckhard; Korfel, Agnieszka

    2010-04-01

    An isolated CNS relapse is rarely seen in acute myeloid leukemia. However, it has a potentially fatal clinical outcome. We herein present the case of a 39-year-old man, who presented to our emergency room with horizontal diplopic images, vertigo, bilateral deafness, and progressing somnolence. Cerebral imaging revealed cerebral and cerebellar edema and a diffuse leukoencephalopathy. With the one-year-old history of an initially successfully treated FAB-M0 acute myeloid leukemia (AML) in mind, a lumbar puncture was carried out that showed a vast number of myeloid blasts in the morphologic analysis of the cerebrospinal fluid. In conjunction with normal findings in the peripheral blood-count with differential and the bone marrow examination a diagnosis of an isolated CNS relapse of the AML was made. Cytarabine chemotherapy was initiated and the symptoms resolved rapidly. To our surprise, cerebral imaging in the course of the treatment not only showed a resolution of the brain edema but also of the leukoencephalopathy, pointing to a direct infiltration of brain parenchyma by leukemic blasts. The case highlights the relevance of the CNS as a pharmacologic "sanctuary" for tumor cells in patients that on prior treatments have not received intrathecal chemotherapy or chemotherapeutics that cross the blood-brain barrier. PMID:18826442

  9. MiR-181 family: regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets.

    PubMed

    Su, R; Lin, H-S; Zhang, X-H; Yin, X-L; Ning, H-M; Liu, B; Zhai, P-F; Gong, J-N; Shen, C; Song, L; Chen, J; Wang, F; Zhao, H-L; Ma, Y-N; Yu, J; Zhang, J-W

    2015-06-01

    MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy. PMID:25174404

  10. Differential regulation of myeloid leukemias by the bone marrow microenvironment.

    PubMed

    Krause, Daniela S; Fulzele, Keertik; Catic, André; Sun, Chia Chi; Dombkowski, David; Hurley, Michael P; Lezeau, Sanon; Attar, Eyal; Wu, Joy Y; Lin, Herbert Y; Divieti-Pajevic, Paola; Hasserjian, Robert P; Schipani, Ernestina; Van Etten, Richard A; Scadden, David T

    2013-11-01

    Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSCs) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow microenvironment (BMM) and may be the cause of relapse following chemotherapy. Targeting the niche is a new strategy to eliminate persistent and drug-resistant LSCs. CD44 (refs. 3,4) and interleukin-6 (ref. 5) have been implicated previously in the LSC niche. Transforming growth factor-β1 (TGF-β1) is released during bone remodeling and plays a part in maintenance of CML LSCs, but a role for TGF-β1 from the BMM has not been defined. Here, we show that alteration of the BMM by osteoblastic cell-specific activation of the parathyroid hormone (PTH) receptor attenuates BCR-ABL1 oncogene-induced CML-like myeloproliferative neoplasia (MPN) but enhances MLL-AF9 oncogene-induced AML in mouse transplantation models, possibly through opposing effects of increased TGF-β1 on the respective LSCs. PTH treatment caused a 15-fold decrease in LSCs in wild-type mice with CML-like MPN and reduced engraftment of immune-deficient mice with primary human CML cells. These results demonstrate that LSC niches in CML and AML are distinct and suggest that modulation of the BMM by PTH may be a feasible strategy to reduce LSCs, a prerequisite for the cure of CML. PMID:24162813

  11. Novel drugs for older patients with acute myeloid leukemia.

    PubMed

    Montalban-Bravo, G; Garcia-Manero, G

    2015-04-01

    Acute myeloid leukemia (AML) is the second most common form of leukemia and the most frequent cause of leukemia-related deaths in the United States. The incidence of AML increases with advancing age and the prognosis for patients with AML worsens substantially with increasing age. Many older patients are ineligible for intensive treatment and require other therapeutic approaches to optimize clinical outcome. To address this treatment gap, novel agents with varying mechanisms of action targeting different cellular processes are currently in development. Hypomethylating agents (azacitidine, decitabine, SGI-110), histone deacetylase inhibitors (vorinostat, pracinostat, panobinostat), FMS-like tyrosine kinase receptor-3 inhibitors (quizartinib, sorafenib, midostaurin, crenolanib), cytotoxic agents (clofarabine, sapacitabine, vosaroxin), cell cycle inhibitors (barasertib, volasertib, rigosertib) and monoclonal antibodies (gentuzumab ozogamicin, lintuzumab-Ac225) represent some of these promising new treatments. This review provides an overview of novel agents that have either completed or are currently in ongoing phase III trials in patients with previously untreated AML for whom intensive treatment is not an option. Other potential drugs in earlier stages of development will also be addressed in this review. PMID:25142817

  12. Sex differences in the incidence of chronic myeloid leukemia.

    PubMed

    Radivoyevitch, Tomas; Jankovic, Gradimir M; Tiu, Ramon V; Saunthararajah, Yogen; Jackson, Robert C; Hlatky, Lynn R; Gale, Robert Peter; Sachs, Rainer K

    2014-03-01

    The incidence of chronic myeloid leukemia (CML), which is caused by BCR/ABL chimeric oncogene formation in a pluripotent hematopoietic stem cell (HSC), increases with age and exposure to ionizing radiation. CML is a comparatively well-characterized neoplasm, important for its own sake and useful for insights into other neoplasms. Here, Surveillance, Epidemiology and End Results (SEER) CML data are analyzed after considering possible misclassification of chronic myelo-monocytic leukemia as CML. For people older than 25 years, plots of male and female CML log incidences versus age at diagnosis are approximately parallel straight lines with males either above or to the left of females. This is consistent with males having a higher risk of developing CML or a shorter latency from initiation to diagnosis of CML. These distinct mechanisms cannot be distinguished using SEER data alone. Therefore, CML risks among male and female Japanese A-bomb survivors are also analyzed. The present analyses suggest that sex differences in CML incidence more likely result from differences in risk than in latency. The simplest but not the sole interpretation of this is that males have more target cells at risk to develop CML. Comprehensive mathematical models of CML could lead to a better understanding of the role of HSCs in CML and other preleukemias that can progress to acute leukemia. PMID:24337217

  13. Sex differences in the incidence of chronic myeloid leukemia

    PubMed Central

    Jankovic, Gradimir M.; Tiu, Ramon V.; Saunthararajah, Yogen; Jackson, Robert C.; Hlatky, Lynn R.; Gale, Robert Peter; Sachs, Rainer K.

    2014-01-01

    The incidence of chronic myeloid leukemia (CML), which is caused by BCR/ABL chimeric oncogene formation in a pluripotent hematopoietic stem cell (HSC), increases with age and exposure to ionizing radiation. CML is a comparatively well-characterized neoplasm, important for its own sake and useful for insights into other neoplasms. Here, Surveillance, Epidemiology and End Results (SEER) CML data are analyzed after considering possible misclassification of chronic myelo-monocytic leukemia as CML. For people older than 25 years, plots of male and female CML log incidences versus age at diagnosis are approximately parallel straight lines with males either above or to the left of females. This is consistent with males having a higher risk of developing CML or a shorter latency from initiation to diagnosis of CML. These distinct mechanisms cannot be distinguished using SEER data alone. Therefore, CML risks among male and female Japanese A-bomb survivors are also analyzed. The present analyses suggest that sex differences in CML incidence more likely result from differences in risk than in latency. The simplest but not the sole interpretation of this is that males have more target cells at risk to develop CML. Comprehensive mathematical models of CML could lead to a better understanding of the role of HSCs in CML and other preleukemias that can progress to acute leukemia. PMID:24337217

  14. Myeloid Cell Nuclear Differentiation Antigen (MNDA) Expression Distinguishes Extramedullary Presentations of Myeloid Leukemia From Blastic Plasmacytoid Dendritic Cell Neoplasm.

    PubMed

    Johnson, Ryan C; Kim, Jinah; Natkunam, Yasodha; Sundram, Uma; Freud, Aharon G; Gammon, Bryan; Cascio, Michael J

    2016-04-01

    Myeloid neoplasms constitute one of the most common malignancies in adults. In most cases these proliferations initially manifest in the blood and marrow; however, extramedullary involvement may precede blood or marrow involvement in a subset of cases, making a definitive diagnosis challenging by morphologic and immunohistochemical assessment alone. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive entity that frequently presents in extramedullary sites and can show morphologic and immunophenotypic overlap with myeloid neoplasms. Given that BPDCN and myeloid neoplasms may both initially present in extramedullary sites and that novel targeted therapies may be developed that exploit the unique molecular signature of BPDCN, new immunophenotypic markers that can reliably separate myeloid neoplasms from BPDCN are desirable. We evaluated the utility of myeloid cell nuclear differentiation antigen (MNDA) expression in a series of extramedullary myeloid leukemias (EMLs) and BPDCN. Forty biopsies containing EML and 19 biopsies containing BPDCN were studied by MNDA immunohistochemistry. The majority of myeloid neoplasms showed nuclear expression of MNDA (65%). In contrast, all cases of BPDCN lacked MNDA expression. These findings show that MNDA is expressed in the majority of EMLs and support the inclusion of MNDA immunohistochemistry in the diagnostic evaluation of blastic hematopoietic infiltrates, particularly when the differential diagnosis is between myeloid leukemia and BPDCN. PMID:26796502

  15. Postmenopausal Bleeding Resulting from Acute Myeloid Leukemia Infiltration of the Endometrium.

    PubMed

    Wasson, Megan; Hochman, Moses; Cadungog, Mark

    2015-07-01

    Postmenopausal bleeding can be the result of numerous etiologies including endometrial carcinoma, vaginal atrophy, and endometrial polyps. Manifestation of a hematologic disease, such as acute myeloid leukemia (AML), is a rare occurrence. A 65-year-old woman with pancytopenia and postmenopausal bleeding was diagnosed with AML. Endometrial biopsy following dilation and curettage of the uterus revealed extensive mononuclear cell infiltrate consistent with AML. The patient was a poor surgical candidate and subsequently underwent treatment with chemotherapy, hormonal therapy, pelvic radiation, and uterine artery embolization to control her vaginal bleeding. A multi-disciplinary approach is necessary for treatment of post-menopausal bleeding resulting from AML infiltration of the endometrium. PMID:26285320

  16. Common and overlapping oncogenic pathways contribute to the evolution of acute myeloid leukemias

    PubMed Central

    Kvinlaug, Brynn T; Chan, Wai-In; Bullinger, Lars; Ramaswami, Mukundhan; Sears, Christopher; Foster, Donna; Lazic, Stanley E; Okabe, Rachel; Benner, Axel; Lee, Benjamin H; De Silva, Inusha; Valk, Peter JM; Delwel, Ruud; Armstrong, Scott A; Döhner, Hartmut; Gilliland, D Gary; Huntly, Brian JP

    2011-01-01

    Fusion oncogenes in acute myeloid leukemia (AML) promote self-renewal from committed progenitors, thereby linking transformation and self-renewal pathways. Like most cancers, AML is a genetically and biologically heterogeneous disease, but it is unclear whether transformation results from common or overlapping genetic programs acting downstream of multiple mutations, or by the engagement of unique genetic programs acting cooperatively downstream of individual mutations. This distinction is important, because the involvement of common programs would imply the existence of common molecular targets to treat AML, no matter which fusion oncogenes are involved. Here we demonstrate that the ability to promote self-renewal is a generalized property of leukemia-associated oncogenes. Disparate oncogenes initiated overlapping transformation and self-renewal gene expression programs, the common elements of which were defined in established leukemia stem cells from an animal model as well as from a large cohort of patients with differing AML subtypes, where they strongly predicted pathobiological character. Notably, individual genes commonly activated in these programs could partially phenocopy the self-renewal function of leukemia-associated oncogenes in committed murine progenitors. Further, they could generate AML following expression in murine bone marrow. In summary, our findings reveal the operation of common programs of self-renewal and transformation downstream of leukemia-associated oncogenes, suggesting mechanistically common therapeutic approaches to AML are likely to be possible, regardless of the identity of the driver oncogene involved. PMID:21505102

  17. Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different Responses to Chemotherapy

    PubMed Central

    Onozawa, Masahiro; Miyashita, Naohiro; Yokohata, Emi; Yoshida, Miho; Kanaya, Minoru; Kosugi-Kanaya, Mizuha; Takemura, Ryo; Takahashi, Shojiro; Sugita, Junichi; Shigematsu, Akio; Takahata, Mutsumi; Fujisawa, Shinichi; Hashimoto, Daigo; Fujimoto, Katsuya; Endo, Tomoyuki; Kondo, Takeshi; Teshima, Takanori

    2016-01-01

    We report a case of acute myeloid leukemia (AML) with two cytogenetically unrelated clones. The patient was a 45-year-old male who was diagnosed with acute monoblastic leukemia (AMoL). Initial G-band analysis showed 51,XY,+6,+8,inv(9)(p12q13)c,+11,+13,+19[12]/52,idem,+Y[8], but G-band analysis after induction therapy showed 45,XY,-7,inv(9)(p12q13)c[19]/46,XY,inv(9)(p12q13)c[1]. Retrospective FISH analysis revealed a cryptic monosomy 7 clone in the initial AML sample. The clone with multiple trisomies was eliminated after induction therapy and never recurred, but a clone with monosomy 7 was still detected in myelodysplastic marrow with a normal blast percentage. Both clones were successfully eliminated after related peripheral blood stem cell transplantation, but the patient died of relapsed AML with monosomy 7. We concluded that one clone was de novo AMoL with chromosome 6, 8, 11, 13, and 19 trisomy and that the other was acute myeloid leukemia with myelodysplasia-related changes(AML-MRC) with chromosome 7 monosomy showing different responses to chemotherapy. Simultaneous onset of cytogenetically unrelated hematological malignancies that each have a different disease status is a rare phenomenon but is important to diagnose for a correct understanding of the disease status and for establishing an appropriate treatment strategy. PMID:27034857

  18. Gene expression profiles in acute myeloid leukemia with common translocations using SAGE

    PubMed Central

    Lee, Sanggyu; Chen, Jianjun; Zhou, Guolin; Shi, Run Zhang; Bouffard, Gerard G.; Kocherginsky, Masha; Ge, Xijin; Sun, Miao; Jayathilaka, Nimanthi; Kim, Yeong Cheol; Emmanuel, Neelmini; Bohlander, Stefan K.; Minden, Mark; Kline, Justin; Ozer, Ozden; Larson, Richard A.; LeBeau, Michelle M.; Green, Eric D.; Trent, Jeffery; Karrison, Theodore; Liu, Piu Paul; Wang, San Ming; Rowley, Janet D.

    2006-01-01

    Identification of the specific cytogenetic abnormality is one of the critical steps for classification of acute myeloblastic leukemia (AML) which influences the selection of appropriate therapy and provides information about disease prognosis. However at present, the genetic complexity of AML is only partially understood. To obtain a comprehensive, unbiased, quantitative measure, we performed serial analysis of gene expression (SAGE) on CD15+ myeloid progenitor cells from 22 AML patients who had four of the most common translocations, namely t(8;21), t(15;17), t(9;11), and inv(16). The quantitative data provide clear evidence that the major change in all these translocation-carrying leukemias is a decrease in expression of the majority of transcripts compared with normal CD15+ cells. From a total of 1,247,535 SAGE tags, we identified 2,604 transcripts whose expression was significantly altered in these leukemias compared with normal myeloid progenitor cells. The gene ontology of the 1,110 transcripts that matched known genes revealed that each translocation had a uniquely altered profile in various functional categories including regulation of transcription, cell cycle, protein synthesis, and apoptosis. Our global analysis of gene expression of common translocations in AML can focus attention on the function of the genes with altered expression for future biological studies as well as highlight genes/pathways for more specifically targeted therapy. PMID:16418266

  19. Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

    PubMed Central

    ESPíRITO SANTO, ANA ESPÍRITO; CHACIM, SÉRGIO; FERREIRA, ISABEL; LEITE, LUÍS; MOREIRA, CLAUDIA; PEREIRA, DULCINEIA; DANTAS BRITO, MARGARIDA DANTAS; NUNES, MARTA; DOMINGUES, NELSON; OLIVEIRA, ISABEL; MOREIRA, ILÍDIA; MARTINS, ANGELO; VITERBO, LUÍSA; MARIZ, JOSÉ MÁRIO; MEDEIROS, RUI

    2016-01-01

    Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified. Data regarding the patient demographics, primary diagnosis and treatment, age at onset of therapy-related myeloid neoplasm, latency time of the neoplasm, cytogenetic characteristics, AML therapy and outcome were collected from medical records. A previous diagnosis with solid tumors was present in 28 patients, and 10 patients possessed a history of hematological conditions, all a lymphoproliferative disorder. Breast cancer was the most frequent solid tumor identified (39.5% of all solid tumors diagnosed). The mean latency time was 3 years. In the present study, t-AML patients were older (P<0.001) and more frequently carried cytogenetic abnormalities (P=0.009) compared with de novo AML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (P<0.001). However, in younger patients (age, <50 years) there was no difference between the overall survival time of patients with t-AML and those with de novo AML (P=0.983). Additionally, patients with promyelocytic leukemia possess a good prognosis, even when AML occurs as a secondary event (P=0.98). To the best of our knowledge, the present study is the first to evaluate t-AML in Portugal and the results are consistent with the data published previously in other populations. The present study concludes that although t-AML demonstrates a poor prognosis, this is not observed among younger patients or promyelocytic leukemia patients. PMID:27347135

  20. ST-Elevation Myocardial Infarction and Myelodysplastic Syndrome with Acute Myeloid Leukemia Transformation

    PubMed Central

    Jao, Geoffrey T.; Knovich, Mary Ann; Savage, Rodney W.; Sane, David C.

    2014-01-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach—balloon angioplasty with the provisional use of bare-metal stents—might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days. PMID:24808792

  1. The artful management of older patients with acute myeloid leukemia.

    PubMed

    Yang, Jay; Schiffer, Charles A

    2016-05-01

    Acute myeloid leukemia in older patients has historically had a dismal 10-15% long-term survival rate. Although patient frailty plays a role in this disappointing outcome, the primary driver of poor results remains the resistance of disease to current therapies. The optimal management of this difficult-to-treat disease should include a careful consideration of disease, patient and treatment factors. Disease factors include cytogenetic and molecular features and the history of an antecedent hematological disorder. Patient factors include age, performance status, comorbid conditions and individual patient preference. We favor intensive induction in most fit older patients but alternatives such as hypomethylating agents and low-dose cytarabine may be considered in patients with other comorbidities. Enrollment of patients into well designed clinical trials addressing important questions remains of utmost importance in order to advance the understanding and treatment of this disease although the best means of drug development remains a challenging dilemma. PMID:26878693

  2. Whole Exome Sequencing of Chronic Myeloid Leukemia Patients

    PubMed Central

    SABRI, Shaghayegh; KEYHANI, Manouchehr; AKBARI, Mohammad Taghi

    2016-01-01

    Background: Previous studies have shown that leukemogenic chromosomal translocations, including fusions between Break point Cluster Region (BCR) and Abelson (ABL) are present in the peripheral blood of healthy individuals. The aim of this study was to gain insights into the genetic alterations other than BCR-Abl translocation in molecular level, which cause chronic myeloid leukemia (CML). Methods: We performed whole-exome sequencing on four cases representative of BCR-ABL positive CML in chronic phase of the disease. Results: We did not identify any pathogenic mutation in all known genes involved in CML or other cancers in our subjects. Nevertheless, we identified polymorphisms in related genes. Conclusion: It is the first report of exome sequencing in Philadelphia chromosome positive CML patients. We did not identify any pathogenic mutation in known cancer genes in our patients who can be due to CML pathogenesis or technical limitations. PMID:27141497

  3. How I treat newly diagnosed chronic myeloid leukemia in 2015.

    PubMed

    Gambacorti-Passerini, Carlo; Piazza, Rocco

    2015-02-01

    The initial treatment for chronic myeloid leukemia in chronic phase (CP-CML) represents a complex process, which includes a prompt and precise diagnosis, the choice among three available tyrosine kinase inhibitors (TKIs), and the initial management of care for these patients, which will protract over a very long period of time. This manuscript summarizes different data on activity, side effects, and supportive measures available for each TKI, the need for particular care in the logistical organization of CML management, the scenario which will be opened by the future availability of generic imatinib. The opinion of the authors is that imatinib remains the first-line treatment for CP-CML; this strategy, accompanied by intensive monitoring and possible dose modification/drug switch after the initial 3-12 months of treatment presently assures a normal life expectancy to the population of newly diagnosed patients with CP-CML. PMID:25370814

  4. Molecular Detection of BCR-ABL in Chronic Myeloid Leukemia.

    PubMed

    Qin, Ya-Zhen; Huang, Xiao-Jun

    2016-01-01

    All chronic myeloid leukemia (CML) patients have the BCR-ABL fusion gene. The constitutively activated BCR-ABL tyrosine kinase is a critical pathogenetic event in CML. Tyrosine kinase inhibitors (TKIs), such as imatinib, are synthesized small molecules that primarily target BCR-ABL tyrosine kinases and have become a first-line treatment for CML. Detection of BCR-ABL transcript level by real-time quantitative polymerase chain reaction (RQ-PCR) is a clinical routine for evaluating TKI treatment efficacy and predicting long-term response. Furthermore, because they are a main TKI resistance mechanism, the BCR-ABL tyrosine kinase domain (TKD) point mutations that are detected by Sanger sequencing can help clinicians make decisions on subsequent treatment selections. Here, we present protocols for the two abovementioned molecular methods for CML analysis. PMID:27581134

  5. Novel Prognostic and Therapeutic Mutations in Acute Myeloid Leukemia.

    PubMed

    Medinger, Michael; Lengerke, Claudia; Passweg, Jakob

    Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence increases with age. Cytogenetics and mutation testing remain important prognostic tools for treatment after induction therapy. The post-induction treatment is dependent on risk stratification. Despite rapid advances in determination of gene mutations involved in the pathophysiology and biology of AML, and the rapid development of new drugs, treatment improvements changed slowly over the past 30 years, with the majority of patients eventually experiencing relapse and dying of their disease. Allogenic hematopoietic stem cell transplantation remains the best chance of cure for patients with intermediate- or high-risk disease. This review gives an overview about advances in prognostic markers and novel treatment options for AML, focusing on new prognostic and probably therapeutic mutations, and novel drug therapies such as tyrosine kinase inhibitors. PMID:27566651

  6. Analogue peptides for the immunotherapy of human acute myeloid leukemia.

    PubMed

    Hofmann, Susanne; Mead, Andrew; Malinovskis, Aleksandrs; Hardwick, Nicola R; Guinn, Barbara-Ann

    2015-11-01

    The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies. PMID:26438084

  7. New approaches for the immunotherapy of Acute Myeloid Leukemia

    PubMed Central

    Geiger, Terrence L.; Rubnitz, Jeffrey E.

    2015-01-01

    Acute Myeloid Leukemia (AML) is a set of related diseases characterized by the immortalization and uncontrolled expansion of myeloid precursors. Core therapy for AML has remained unchanged for nearly 30 years, and survival rates remain unsatisfactory. However, advances in the immunotherapy of AML have created opportunities for improved outcomes. Enforcing a tumor-specific immune response through the re-direction of the adaptive immune system, which links remarkable specificity with potent cytotoxic effector functions, has proven particularly compelling. This may be coupled with immune checkpoint blockade and conventional therapies for optimal effect. Engineered antibodies are currently in use in AML and the repertoire of available therapeutics will expand. NK cells have shown effectiveness in this disease. New methods to optimize the targeting and activation of AML cells show potential. Most significantly, adoptive immunotherapy with tumor-specific T cells, and particularly T cells re-directed using genetically introduced TCR or chimeric antigen receptors, have particular promise. Each of these approaches has unique benefits and challenges that we explore in this review. PMID:25977190

  8. Brachial Plexopathy due to Myeloid Sarcoma in a Patient With Acute Myeloid Leukemia After Allogenic Peripheral Blood Stem Cell Transplantation.

    PubMed

    Ha, Yumi; Sung, Duk Hyun; Park, Yoonhong; Kim, Du Hwan

    2013-04-01

    Myeloid sarcoma is a solid, extramedullary tumor comprising of immature myeloid cells. It may occur in any organ; however, the invasion of peripheral nervous system is rare. Herein, we report the case of myeloid sarcoma on the brachial plexus. A 37-year-old woman with acute myelogenous leukemia achieved complete remission after chemotherapy. One year later, she presented right shoulder pain, progressive weakness in the right upper extremity and hypesthesia. Based on magnetic resonance images (MRI) and electrophysiologic study, a provisional diagnosis of brachial plexus neuritis was done and hence steroid pulse therapy was carried out. Three months later the patient presented epigastric pain. After upper gastrointestinal endoscopy, myeloid sarcoma of gastrointestinal tract was confirmed pathologically. Moreover, 18-fluoride fluorodeoxyglucose positron emission tomography showed a fusiform shaped mass lesion at the brachial plexus overlapping with previous high signal lesion on the MRI. Therefore, we concluded the final diagnosis as brachial plexopathy due to myeloid sarcoma. PMID:23705126

  9. Karyotype complexity and prognosis in acute myeloid leukemia

    PubMed Central

    Stölzel, F; Mohr, B; Kramer, M; Oelschlägel, U; Bochtler, T; Berdel, W E; Kaufmann, M; Baldus, C D; Schäfer-Eckart, K; Stuhlmann, R; Einsele, H; Krause, S W; Serve, H; Hänel, M; Herbst, R; Neubauer, A; Sohlbach, K; Mayer, J; Middeke, J M; Platzbecker, U; Schaich, M; Krämer, A; Röllig, C; Schetelig, J; Bornhäuser, M; Ehninger, G

    2016-01-01

    A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype. PMID:26771812

  10. An update of current treatments for adult acute myeloid leukemia

    PubMed Central

    Gardin, Claude

    2016-01-01

    Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents. PMID:26660429