blast crisis

Summary

Summary: Rapid increase in the proportion of blast cells in the blood and bone marrow.

Top Publications

  1. ncbi Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
    Catriona H M Jamieson
    Division of Hematology, Stanford University School of Medicine, Stanford, Calif 94305 5323, USA
    N Engl J Med 351:657-67. 2004
  2. ncbi The biology of CML blast crisis
    Bruno Calabretta
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
    Blood 103:4010-22. 2004
  3. ncbi Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression
    A Sengupta
    Structural Genomics Section and Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, West Bengal, India
    Leukemia 21:949-55. 2007
  4. ncbi The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein
    Paolo Neviani
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA
    Cancer Cell 8:355-68. 2005
  5. pmc Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation
    Annelie E Abrahamsson
    Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:3925-9. 2009
  6. ncbi p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells
    L F Peterson
    Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
    Leukemia 25:761-9. 2011
  7. pmc A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9
    Ajeeta B Dash
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:7622-7. 2002
  8. pmc FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia
    Paolo Neviani
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA
    J Clin Invest 117:2408-21. 2007
  9. pmc Triptolide induces cell death independent of cellular responses to imatinib in blast crisis chronic myelogenous leukemia cells including quiescent CD34+ primitive progenitor cells
    Duncan H Mak
    Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cancer Ther 8:2509-16. 2009
  10. ncbi Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia
    Fumio Nakahara
    Department of Cell Therapy and Transplantation Medicine, University of Tokyo, Tokyo, Japan
    Blood 115:2872-81. 2010

Detail Information

Publications238 found, 100 shown here

  1. ncbi Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
    Catriona H M Jamieson
    Division of Hematology, Stanford University School of Medicine, Stanford, Calif 94305 5323, USA
    N Engl J Med 351:657-67. 2004
    The progression of chronic myelogenous leukemia (CML) to blast crisis is supported by self-renewing leukemic stem cells. In normal mouse hematopoietic stem cells, the process of self-renewal involves the beta-catenin-signaling pathway...
  2. ncbi The biology of CML blast crisis
    Bruno Calabretta
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
    Blood 103:4010-22. 2004
    ..evolves from a chronic phase characterized by the Philadelphia chromosome as the sole genetic abnormality into blast crisis, which is often associated with additional chromosomal and molecular secondary changes...
  3. ncbi Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression
    A Sengupta
    Structural Genomics Section and Biophysics Division, Saha Institute of Nuclear Physics, Kolkata, West Bengal, India
    Leukemia 21:949-55. 2007
    ..CML stem-cell compartment is dynamic as it progresses to terminal blast crisis where myeloid and lymphoid blasts fail to differentiate...
  4. ncbi The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein
    Paolo Neviani
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA
    Cancer Cell 8:355-68. 2005
    ..We show here that, in BCR/ABL-transformed cells and CML blast crisis (CML-BC) progenitors, the phosphatase activity of the tumor suppressor PP2A is inhibited by the BCR/ABL-induced ..
  5. pmc Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation
    Annelie E Abrahamsson
    Department of Medicine and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:3925-9. 2009
    ..from a chronic phase (CP) in hematopoietic stem cells (HSC) that harbor the BCR-ABL translocation, to blast crisis (BC), characterized by aberrant activation of beta-catenin within granulocyte-macrophage progenitors (GMP)...
  6. ncbi p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells
    L F Peterson
    Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
    Leukemia 25:761-9. 2011
    ..with MI-219-a novel compound, and consequently p53 stabilization induce chronic myeloid leukemia (CML) blast crisis cells to undergo apoptosis regardless of the presence of the T315I mutation in the BCR-ABL kinase domain...
  7. pmc A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9
    Ajeeta B Dash
    Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:7622-7. 2002
    ..Progression of CML to acute leukemia (blast crisis) in humans has been associated with acquisition of secondary chromosomal translocations, including the t(7;11)(..
  8. pmc FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia
    Paolo Neviani
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA
    J Clin Invest 117:2408-21. 2007
    b>Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive (Ph1-positive) acute lymphocytic leukemia (ALL) are 2 fatal BCR/ABL-driven leukemias against which Abl kinase inhibitors fail to induce a long-term ..
  9. pmc Triptolide induces cell death independent of cellular responses to imatinib in blast crisis chronic myelogenous leukemia cells including quiescent CD34+ primitive progenitor cells
    Duncan H Mak
    Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cancer Ther 8:2509-16. 2009
    ..However, resistance evolves due to BCR-ABL mutations and other mechanisms. Furthermore, patients with blast crisis CML are less responsive and quiescent CML stem cells are insensitive to these inhibitors...
  10. ncbi Hes1 immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia
    Fumio Nakahara
    Department of Cell Therapy and Transplantation Medicine, University of Tokyo, Tokyo, Japan
    Blood 115:2872-81. 2010
    ..to irradiated mice, the combination of Hes1 and BCR-ABL in CMPs and GMPs caused acute leukemia resembling blast crisis of chronic myelogenous leukemia (CML), resulting in rapid death of the recipient mice...
  11. pmc Predictors of primary imatinib resistance in chronic myelogenous leukemia are distinct from those in secondary imatinib resistance
    Wenyong W Zhang
    Department of Pathology, Baylor College of Medicine, Houston TX, USA
    J Clin Oncol 27:3642-9. 2009
    ..Such primary imatinib resistance is distinguished from secondary resistance which reemerges after attainment of cytogenetic remission...
  12. pmc The derivation of diagnostic markers of chronic myeloid leukemia progression from microarray data
    Vivian G Oehler
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Blood 114:3292-8. 2009
    ..identified 6 genes (NOB1, DDX47, IGSF2, LTB4R, SCARB1, and SLC25A3) that discriminated chronic phase (CP) from blast crisis (BC) CML. In CML, phase labels divide disease progression into discrete states...
  13. pmc A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation
    Mario Notari
    Human Cancer Genetics Program, The Ohio State University Medical Center, Columbus, OH 43240, USA
    Blood 107:2507-16. 2006
    Altered mRNA translation is one of the effects exerted by the BCR/ABL oncoprotein in the blast crisis phase of chronic myelogenous leukemia (CML)...
  14. pmc Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function
    Sharon Lim
    Cancer and Stem Cell Biology Program, Duke National University of Singapore Graduate Medical School, Singapore 169857
    Proc Natl Acad Sci U S A 110:E2298-307. 2013
    ..the oncogenic fusion protein BCR-ABL1 in chronic phase, but is resistant to treatment after it progresses to blast crisis (BC)...
  15. pmc β-Arrestin2 mediates the initiation and progression of myeloid leukemia
    Mark Fereshteh
    Department of Pharmacology, University of California, San Diego School of Medicine and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92093
    Proc Natl Acad Sci U S A 109:12532-7. 2012
    ..preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML)...
  16. ncbi Development of acute lymphoblastic leukemia and myeloproliferative disorder in transgenic mice expressing p210bcr/abl: a novel transgenic model for human Ph1-positive leukemias
    H Honda
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan
    Blood 91:2067-75. 1998
    ..MPD mouse showed remarkable proliferation of blast cells in the lung, which might represent an extramedullar blast crisis. The results demonstrate that the expression of p210bcr/abl in hematopoietic progenitor cells in transgenic ..
  17. pmc CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia
    Hideki Makishima
    Department of Translational Hematology and Oncology Research, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA
    Blood 117:e198-206. 2011
    ..2 and 21q22.12 involved tumor associated genes NF1 and RUNX1, respectively. Our results indicate that CBL family, TET2, ASXL1, and IDH family mutations and additional cryptic karyotypic abnormalities can occur in advanced phase CML...
  18. pmc The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia
    Lars Klemm
    Leukemia and Lymphoma Program, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90027, USA
    Cancer Cell 16:232-45. 2009
    ..until leukemia cells acquire drug resistance through BCR-ABL1 mutations and progress into fatal B lymphoid blast crisis (LBC). Despite its clinical significance, the mechanism of progression into LBC is unknown...
  19. ncbi Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1038-42. 2001
    ..in patients in the chronic phase, we evaluated STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase, in patients who had CML in blast crisis and in patients with ALL who had the Ph chromosome.
  20. ncbi Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia
    Kazuko Miyazaki
    Department of Developmental Biology, Research Institute of Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
    Blood 113:4702-10. 2009
    ..from p210BCR/ABL-transformed stem cells, which begins as indolent chronic phase (CP) but progresses into fatal blast crisis (BC)...
  21. ncbi Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow
    W S Pear
    Department of Pathology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, USA
    Blood 92:3780-92. 1998
    ..The disease in many of these mice has progressed to the development of acute lymphoma/leukemia resembling blast crisis. These results demonstrate that murine CML recapitulates important features of human CML...
  22. ncbi Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis
    C Zheng
    III Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Ruprecht Karls Universität Heidelberg, Mannheim, Germany
    Leukemia 20:1028-34. 2006
    ..Our data suggest the existence of a common gene expression profile of CML-BP and provide new insight into the molecular phenotype of blasts associated with disease progression and high malignancy...
  23. ncbi Myeloid blast crisis evolving during imatinib treatment of an FIP1L1-PDGFR alpha-positive chronic myeloproliferative disease with prominent eosinophilia
    N von Bubnoff
    Leukemia 19:286-7. 2005
  24. pmc IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
    A Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Leukemia 24:1302-9. 2010
    ..The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes...
  25. ncbi An acute myeloid leukemia M6b blast crisis with giant proerythroblasts in chronic myeloid leukemia
    Prashant Sharma
    Department of Pathology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
    J Pediatr Hematol Oncol 31:220-1. 2009
    ..bcr-abl positive chronic myeloid leukemia who subsequently developed a fatal AML-M6b (pure erythroleukemia) blast crisis is presented...
  26. ncbi Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia
    Li Juan Zhao
    State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Rui Jin Hospital, Shanghai, China
    Blood 119:2873-82. 2012
    ..disorder status at the chronic phase of the disease, but progression from the chronic phase to blast crisis (BC) is believed to require additional mutations...
  27. ncbi Depsipeptide (FK228) preferentially induces apoptosis in BCR/ABL-expressing cell lines and cells from patients with chronic myelogenous leukemia in blast crisis
    Seiichi Okabe
    First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan
    Stem Cells Dev 16:503-14. 2007
    ..FK228) in BCR/ABL-expressing cell lines and its effectiveness in imatinib-resistant cells from patients with blast crisis of CML. FK228 potently induced apoptosis of TF-1 BCR/ABL, K562, and H7 BCR/ABL cells...
  28. ncbi Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors
    Ronald L Paquette
    UCLA Department of Medicine, Los Angeles, CA, USA
    Cancer Genet 204:392-7. 2011
    ..1 (EVI1) translocations were evaluated in 42 consecutive chronic myeloid leukemia (CML) patients in myeloid blast crisis (MBC)...
  29. ncbi RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance
    Catherine Roche-Lestienne
    Cancer Research Institute of Lille, JP Aubert Center, Inserm Unit 837, France
    Blood 111:3735-41. 2008
    ..acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1...
  30. ncbi Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up
    Francesca Palandri
    Institute of Hematology and Medical Oncology L and A Seragnoli, S Orsola Malpighi Hospital, University of Bologna, Bologna, Italy
    Haematologica 93:1792-6. 2008
    ..In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients...
  31. ncbi Expression of the NUP98/HOXA9 fusion transcript in the blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia with t(7;11)(p15;p15)
    K Yamamoto
    Department of Haematology, Dokkyo University School of Medicine, Tochigi, Japan
    Br J Haematol 109:423-6. 2000
    ..At the diagnosis of myeloid blast crisis, the karyotype evolved to 46, XY, t(7;11)(p15;p15), t(9;22)(q34;q11)...
  32. ncbi Cadherin-13 in primary and blast crisis chronic myeloid leukaemia: declining expression and negative correlation with the BCR/ABL fusion gene
    H J Mu
    Central Laboratory, Wuxi People s Hospital, Affiliated Nanjing Medical University, PR China
    Br J Biomed Sci 66:20-4. 2009
    ..gene is investigated in peripheral blood from 30 healthy adults, 25 primary CML patients and 25 CML patients in blast crisis using the EvaGreen real-time reverse transcriptase polymerase chain reaction (RT-PCR)...
  33. ncbi Expanding Nilotinib Access in Clinical Trials (ENACT), an open-label multicenter study of oral nilotinib in adult patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase or blast crisis
    Franck E Nicolini
    Hopital Edouard Herriot, Lyon, France
    Leuk Lymphoma 53:907-14. 2012
    ..Reported here are the efficacy and safety data for patients in CML-AP (n = 181) or blast crisis (CML-BC) (n = 190; myeloid BC, 133; lymphoid BC, 50; unknown, seven) enrolled in an expanded access phase IIIb ..
  34. pmc Activation of apoptosis signaling eliminates CD34+ progenitor cells in blast crisis CML independent of response to tyrosine kinase inhibitors
    D H Mak
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Leukemia 26:788-94. 2012
    ..CML), imatinib not only is inactive against quiescent CML stem cells, but also has limited activity against blast crisis (BC) CML...
  35. pmc BCR-ABL1 mediates up-regulation of Fyn in chronic myelogenous leukemia
    Kechen Ban
    Department of Pediatrics Research, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Blood 111:2904-8. 2008
    Chronic myelogenous leukemia (CML) invariably progresses to blast crisis, which represents the most proliferative phase of the disease...
  36. ncbi Therapy of refractory/relapsed acute myeloid leukemia and blast crisis of chronic myeloid leukemia with the combination of cytosine arabinoside, tetrahydrouridine, and carboplatin
    J H Marsh
    Don Monti Division of Oncology Hematology, Department of Medicine, North Shore University Hospital, Manhasset, NY 11030
    Cancer Chemother Pharmacol 31:481-4. 1993
    Eight patients, of whom four had acute myeloid leukemia (AML) and four had chronic myeloid leukemia (CML) blast crisis, were treated with a combination of cytosine arabinoside (ARA-C: 1,600 mg/m2 in three patients, 1,200 mg/m2 in five ..
  37. ncbi Isolated blast crisis in CNS in a patient with chronic myelogenous leukemia maintaining major cytogenetic response after imatinib
    Hyun Jung Kim
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    J Clin Oncol 24:4028-9. 2006
  38. ncbi Haploinsufficiency and acquired loss of Bcl11b and H2AX induces blast crisis of chronic myelogenous leukemia in a transgenic mouse model
    Akiko Nagamachi
    Department of Molecular Oncology, Research Institute of Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
    Cancer Sci 100:1219-26. 2009
    ..is a hematological malignancy that begins as indolent chronic phase (CP) but inevitably progresses to fatal blast crisis (BC)...
  39. ncbi Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study
    Charles L Sawyers
    Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Blood 99:3530-9. 2002
    b>Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy...
  40. ncbi BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571
    Nicholas J Donato
    Department of Bioimmunotherapy, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Blood 101:690-8. 2003
    ..Together, these results suggest that acquired STI571 resistance may be associated with BCR-ABL independence and mediated in part through overexpression of other tyrosine kinases...
  41. ncbi Isolated central nervous system blast crisis in chronic myeloid leukemia
    Senthil Rajappa
    Department of Medical Oncology, Nizam s Institute of Medical Sciences, Punjagutta, Hyderabad, India
    Hematol Oncol 22:179-81. 2004
    ..Extramedullary blast crisis is a rare event...
  42. ncbi Extramedullary blast crisis derived from 2 different clones in the central nervous system and neck during complete cytogenetic remission of chronic myelogenous leukemia treated with imatinib mesylate
    Mitsuhiro Matsuda
    Division of Hematology, Nephrology and Rheumatology, Department of Internal Medicine, Kinki University School of Medicine, Osaka 589 8511, Japan
    Int J Hematol 81:307-9. 2005
    ..with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed an extramedullary blast crisis in the central nervous system (CNS) and then a subcutaneous tumor of the neck during treatment with imatinib ..
  43. ncbi Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells
    Ramadevi Nimmanapalli
    Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute University of South Florida, Tampa, Florida 33614, USA
    Cancer Res 63:5126-35. 2003
    ..of histone deacetylases, depleted the mRNA and protein expression of Bcr-Abl in human chronic myeloid leukemia blast crisis (CML-BC) cells...
  44. ncbi Bcr-Abl expression levels determine the rate of development of resistance to imatinib mesylate in chronic myeloid leukemia
    David J Barnes
    Department of Haematology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom
    Cancer Res 65:8912-9. 2005
    ..its continuous administration is associated with development of resistance, particularly in advanced phase or blast crisis. We investigate here whether a feature of disease progression (i.e...
  45. ncbi Isolated central nervous system relapse in lymphoid blast crisis chronic myeloid leukemia and acute lymphoblastic leukemia in patients on imatinib therapy
    Salha Bujassoum
    Division of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Ontario Canada
    Leuk Lymphoma 45:401-3. 2004
    ..Both patients went on to achieve CNS remission following treatment with intrathecal methotrexate and cytarabine...
  46. ncbi Chronic myelogenous leukemia molecular signature
    Michal Oskar Nowicki
    Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
    Oncogene 22:3952-63. 2003
    ..Interestingly, CML-blast crisis cells in peripheral blood differ from those from bone marrow, indicating major changes in gene expression ..
  47. ncbi Additional clonal abnormalities in Philadelphia-positive ALL and CML demonstrate a different cytogenetic pattern at diagnosis and follow different pathways at progression
    Ulrike Bacher
    Laboratory for Leukemia Diagnostics, Department for Internal Medicine III, Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistrasse 15, D 81377 Munich, Germany
    Cancer Genet Cytogenet 157:53-61. 2005
    ..In addition, the investigation of 10 cases of lymphoid blast crisis of CML showed significant differences in the karyotype in comparison to Ph+ ALL at diagnosis...
  48. ncbi ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chr
    Simona Soverini
    Institute of Hematology and Medical Oncology Seragnoli, University of Bologna, Via Massarenti 9 40138 Bologna, Italy
    J Clin Oncol 23:4100-9. 2005
    ....
  49. ncbi BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2
    Danilo Perrotti
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Nat Genet 30:48-58. 2002
    The arrest of differentiation is a feature of both chronic myelogenous leukemia cells in myeloid blast crisis and myeloid precursors that ectopically express the p210BCR-ABL oncoprotein; however, its underlying mechanisms remain poorly ..
  50. ncbi Chronic myelogenous leukemia: mechanisms underlying disease progression
    A S Shet
    Stem Cell Institute and Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
    Leukemia 16:1402-11. 2002
    ..Disease progression and blast crisis CML is associated with characteristic non-random cytogenetic and molecular events...
  51. pmc ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia
    D Perrotti
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    Br J Cancer 95:775-81. 2006
    ..However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy...
  52. ncbi Megakaryocytic blast crisis as a presenting manifestation of chronic myeloid leukemia
    Sheeja T Pullarkat
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
    Leuk Res 32:1770-5. 2008
    ..either de novo or by transformation of a preexisting myelodysplastic or myeloproliferative process including blast crisis of chronic myeloid leukemia (CML)...
  53. ncbi Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia
    Ali Al-Shehri
    Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
    Hematol Oncol Stem Cell Ther 3:42-6. 2010
    Patients with chronic myeloid leukemia (CML) infrequently present in blast crisis (BC). While most BC are of myeloid origin, megakaryocytic BC is rare, especially at the time of CML diagnosis...
  54. ncbi Chronic myeloid leukemia blast crisis arises from progenitors
    Franziska Michor
    Harvard University, Society of Fellows, 78 Mt Auburn Street, Cambridge, Massachusetts 02138, USA
    Stem Cells 25:1114-8. 2007
    ..myeloid leukemia (CML) progresses through three distinct clinical stages: chronic phase, accelerated phase, and blast crisis. The progression to accelerated phase and blast crisis is driven by activation of oncogenes, inactivation of ..
  55. ncbi Apoptotic and antiproliferative effects of gemcitabine and gemcitabine plus Ara-C on blast cells from patients with blast crisis chronic myeloproliferative disorders
    V Santini
    Department of Hematology, University of Florence Azienda Ospedaliera Careggi, Firenze, Italy
    Haematologica 82:11-5. 1997
    ..We already showed that gemcitabine is active in inhibiting proliferation and inducing apoptosis of HL60 cells...
  56. ncbi Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia
    L Campiotti
    Dipartimento di Medicina Clinica Università dell Insubria, Varese, Italy
    Am J Hematol 82:231-3. 2007
    We describe an extremely rare case of megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. The patient had a very high platelet count and developed an ischemic stroke with seizures...
  57. ncbi Megakaryocytic blast crisis as a first presentation of chronic myeloid leukemia
    Luis Arthur Flores Pelloso
    Disciplina de Hematologia e Hemoterapia, Universidade Federal de Sao Paulo, Brazil
    Eur J Haematol 69:58-61. 2002
    Acute megakaryocytic leukemia (AmegL) corresponds to 5.0-10.0% of all acute myeloid leukemias (AML). Blast crisis as the first presentation of chronic myeloid leukemia (CML) accounts for 10.0% of all cases.
  58. ncbi Aberrant expression of the LHX4 LIM-homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis
    Mitsuko Yamaguchi
    Department of Hematology and Oncology, Tokyo Medical and Dental University, Tokyo, Japan
    Genes Chromosomes Cancer 38:269-73. 2003
    ..chromosome in chronic myelogenous leukemia (CML) are likely to be involved in disease progression to the blast crisis. We describe here a t(1;14)(q25;q32) as an additional chromosomal aberration in a patient with CML in ..
  59. pmc Class II-associated invariant chain peptide down-modulation enhances the immunogenicity of myeloid leukemic blasts resulting in increased CD4+ T-cell responses
    Marvin M van Luijn
    Department of Hematology, VU Institute for Cancer and Immunology, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
    Haematologica 95:485-93. 2010
    ..The current study investigates the role of aberrant HLA class II antigen presentation on leukemic blasts by determining both the clinical and functional impact of the class II-associated invariant chain peptide (CLIP)...
  60. ncbi Indoleamine 2,3-dioxygenase activity of acute myeloid leukemia cells can be measured from patients' sera by HPLC and is inducible by IFN-gamma
    Selim Corm
    INSERM, Unité 837, Equipe 3, Institut de Recherche sur le Cancer de Lille, Lille, France
    Leuk Res 33:490-4. 2009
    ..Thus, in AML, the activity of IDO can be easily monitored, providing a tool for future clinical testing of IDO-blocking drugs...
  61. ncbi Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571)
    Jose F Leis
    Oregon Health and Sciences University, Adult Bone Marrow Transplant Program, Portland, OR 97201, USA
    Leuk Lymphoma 45:695-8. 2004
    ..8%) with chronic myeloid leukemia (CML) lymphoid blast crisis (2), Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL) (2) or CML with biphenotypic ..
  62. ncbi BCR/ABL amplification in chronic myelocytic leukemia blast crisis following imatinib mesylate administration
    Lynda J Campbell
    Victorian Cancer Cytogenetics Service, St Vincent s Hospital, Melbourne, Fitzroy VIC 3065, Australia
    Cancer Genet Cytogenet 139:30-3. 2002
    The onset of accelerated phase or blast crisis of chronic myelocytic leukemia (CML) is usually associated with the acquisition of new chromosome abnormalities in addition to the t(9;22)(q34;q11) that is characteristic of the chronic phase ..
  63. ncbi Imatinib mesylate-sensitive blast crisis immediately after discontinuation of imatinib mesylate therapy in chronic myelogenous leukemia: report of two cases
    Takehiro Higashi
    First Department Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1 1 Iseigaoka, Yahatanishi ku, Kitakyushu 807 8555, Japan
    Am J Hematol 76:275-8. 2004
    ..We here report two CML patients who had imatinib mesylate-sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy...
  64. ncbi Amplification of BCR-ABL and t(3;21) in a patient with blast crisis of chronic myelogenous leukemia
    Chin Lee Phan
    Department of Hematology, Hospital Ampang, Jalan Megah Utara, Pandan Mewah, 68000 Ampang, Selangor, Malaysia
    Cancer Genet Cytogenet 180:60-4. 2008
    ..CML is clinically characterized by three distinct phases: chronic, accelerated, and blast phase. Blast crisis is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or ..
  65. ncbi Chronic myeloid leukaemia as a model of disease evolution in human cancer
    Junia V Melo
    Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    Nat Rev Cancer 7:441-53. 2007
    ..If not cured at this stage, CML invariably progresses and transforms into an acute-type leukaemia undergoing a 'blast crisis'. The causes of this transformation are still poorly understood...
  66. ncbi Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis
    Jorge Cortes
    M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Blood 109:3207-13. 2007
    The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor...
  67. ncbi Genomic imbalances in CML blast crisis: 8q24.12-q24.13 segment identified as a common region of over-representation
    Susan M Gribble
    Department of Haematology, University of Cambridge, Cambridge, United Kingdom
    Genes Chromosomes Cancer 37:346-58. 2003
    ..of complex chromosome markers in 10 CML-derived cell lines after our investigations of CML patients in blast crisis. Multicolor fluorescence in situ hybridization identified a multitude of structural chromosome aberrations...
  68. ncbi Phenotypic and gene expression diversity of malignant cells in human blast crisis chronic myeloid leukemia
    Masha Simanovsky
    Division of Hematology and Bone Marrow Transplantation, Laboratory of Molecular Immunobiology, Chaim Sheba Medical Center, Tel Hashomer, Israel
    Differentiation 76:908-22. 2008
    ..It is believed that in the blast crisis (BC) terminal phase of the disease, blood-circulating blasts represent an expansion of a single CML clone...
  69. ncbi Abnormal centrosome-centriole cycle in chronic myeloid leukaemia?
    Hetal Patel
    Faculty of Medicine, Department of Haematology, Imperial College, Hammersmith Campus, London, UK
    Br J Haematol 146:408-17. 2009
    ..Primary cells from CML blast crisis (BC) patients exhibited a distinctive amorphous staining pattern of pericentrin compared to normal and CML ..
  70. ncbi CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid
    Martin Bornhauser
    Med Klinik und Poliklinik I, Universitatsklinikum Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany
    Ann Hematol 83:401-2. 2004
    ..We report the case of a patient who unexpectedly experienced blast crisis of the central nervous system although having achieved complete cytogenetic remission in the bone marrow...
  71. ncbi Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature
    Matthew R Naunheim
    Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Clin Neurol Neurosurg 112:575-7. 2010
    ..lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then ..
  72. pmc Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia
    K Mitani
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
    EMBO J 13:504-10. 1994
    ....
  73. ncbi HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase
    Huang Xiao-Jun
    Peking University Institute of Hematology, People s Hospital, Beijing, China
    Ann Med 40:444-55. 2008
    ..Recently, we developed an effective method for haploidentical allo-HSCT achieving comparable outcomes to HLA-identical transplantation...
  74. ncbi Successful allogeneic stem cell transplantation in second chronic-phase CML induced by the tyrosine kinase inhibitor nilotinib (AMN107) after blast crisis under imatinib
    H Menzel
    Bone Marrow Transplant 40:83-4. 2007
  75. ncbi High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia
    D Rea
    Service d Hematologie Clinique, Hopital Saint Louis, Paris, France
    Leukemia 20:400-3. 2006
    ..Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled...
  76. ncbi Stem cell regulation and the development of blast crisis in chronic myeloid leukemia: Implications for the outcome of Imatinib treatment and discontinuation
    Dominik Wodarz
    Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697, USA
    Med Hypotheses 70:128-36. 2008
    ..During the accelerated phase and blast crisis, the population of CML cells and the fraction of immature cells rises sharply...
  77. pmc Leukemia stem cells in a genetically defined murine model of blast-crisis CML
    Sarah J Neering
    James P Wilmot Cancer Center, University of Rochester Medical Center, NY 14642, USA
    Blood 110:2578-85. 2007
    ..Taken together, the system provides a powerful means by which the in vivo behavior of LSCs versus HSCs can be characterized and candidate treatment regimens can be optimized for maximal specificity toward primitive leukemia cells...
  78. ncbi ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis
    Tomasz Sacha
    Department of Haematology, Jagiellonian University Medical College, Cracow, Poland
    Leuk Res 27:1163-6. 2003
    ..ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation...
  79. ncbi Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase
    Hagop M Kantarjian
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Blood 99:3547-53. 2002
    ..04), and lower 4-week induction mortality (4% versus 15%, P =.07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML...
  80. ncbi Case of chronic-phase chronic myelogenous leukemia with an abdominal hematopoietic tumor of leukemic clone origin
    Miho Sakakura
    Second Department of Internal Medicine, Mie University School of Medicine, Mie, Japan
    Am J Hematol 77:167-70. 2004
    ..generally indicates a poor prognosis, because it commonly consists of blast proliferation and is followed by blast crisis in the marrow within a few months...
  81. ncbi Chronic myelogenous leukemia--identifying the hydra's heads
    Michael F Clarke
    Department of Medicine, University of Michigan Medical School, Ann Arbor, USA
    N Engl J Med 351:634-6. 2004
  82. ncbi Sustained cytogenetic remission induced by imatinib mesylate in a chronic myeloid leukemia patient who had a relapse into lymphoid crisis after allogeneic hematopoietic stem cell transplantation
    Toshiaki Yujiri
    Third Department of Internal Medicine, Yamaguchi University School of Medicine, Minamikogushi, Ube, Yamaguchi, Japan
    Int J Hematol 80:67-9. 2004
    ..This case highlights the ability of imatinib to induce sustained hematologic and cytogenetic remission in some patients who have had relapses into advanced-stage chronic myeloid leukemia after alloHSCT...
  83. ncbi Imatinib induces a cytogenetic response in blast crisis or interferon failure chronic myeloid leukemia patients with e19a2 BCR-ABL transcripts
    J J Lee
    Leukemia 18:1539-40. 2004
  84. ncbi BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors
    Mhairi Copland
    Section of Experimental Haematology and Haemopoietic Stem Cells, Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Glasgow, United Kingdom
    Blood 111:2843-53. 2008
    ..BMS-214662 was cytotoxic against CML blast crisis stem/progenitor cells, particularly in combination with a tyrosine kinase inhibitor and equally effective in ..
  85. pmc Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice
    Yiguo Hu
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Proc Natl Acad Sci U S A 103:16870-5. 2006
    ..myeloid leukemia (CML) in chronic phase but not Ph(+) B cell acute lymphoblastic leukemia (B-ALL) and CML blast crisis. We find that SRC kinases activated by BCR-ABL remain fully active in imatinib-treated mouse leukemic cells, ..
  86. ncbi Regulation and targeting of Eg5, a mitotic motor protein in blast crisis CML: overcoming imatinib resistance
    Bing Z Carter
    The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cell Cycle 5:2223-9. 2006
    Patients with blast crisis (BC) CML frequently become resistant to Imatinib, a Bcr-Abl tyrosine kinase-targeting agent...
  87. ncbi [Efficacy of imatinib mesylate, a specific inhibitor of BCR/ABL tyrosine kinase, on chronic myeloid leukemia in blast phase]
    Guo Cai Zhang
    Department of Hematology, The First Affiliated Hospital, Sun Yat Sen University, Guangzhou, Guangdong 510080, P R China
    Ai Zheng 23:1696-9. 2004
    ..Chronic myeloid leukemia (CML) in blast phase is refractory with a poor prognosis. This study was to evaluate efficacy of imatinib mesylate, a specific inhibitor of BCR/ABL tyrosine kinase, on CML in blast phase...
  88. ncbi Distinct biological impact of dephosphorylation vs. downregulation of p210Bcr-Abl: implications for imatinib mesylate response and resistance
    Razelle Kurzrock
    Division of Cancer Medicine, The University of Texas, M D Anderson Cancver Center, Houston, Texas 77230 1402, USA
    Leuk Lymphoma 47:1651-64. 2006
    ..We studied K562 cells [chronic myelogenous leukemia (CML) blast crisis line] and MO7E/MBA-1 cells (with MBA-1 cells representing MO7E cells stably transfected with BCR-ABL)...
  89. ncbi Chronic myeloid leukemia presenting with extramedullary disease as massive ascites responding to imatinib mesylate
    Aamer Aleem
    Department of Medicine, Hematology Oncology Division, King Khalid University Hospital, Riyadh, Saudi Arabia
    Leuk Lymphoma 46:1097-9. 2005
    ..This usually occurs during the accelerated phase or blast crisis. We describe a patient who presented with massive ascites probably due to mesenteric/peritoneal infiltration ..
  90. ncbi Sudden blastic transformation in patients with chronic myeloid leukemia treated with imatinib mesylate
    Elias Jabbour
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 107:480-2. 2006
    ..SBT is still a rare event, probably less common than that observed with IFN-alpha therapy. Continuous monitoring of patients treated with imatinib is mandatory...
  91. ncbi Differences between in vivo and in vitro sensitivity to imatinib of Bcr/Abl+ cells obtained from leukemic patients
    Carlo B Gambacorti-Passerini
    Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy
    Blood Cells Mol Dis 28:361-72. 2002
    ..The in vivo effects of imatinib were evaluated in 12 CML (chronic myeloid leukemia) patients in blast crisis or accelerated phase who were treated with imatinib...
  92. pmc Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells
    Geoffrey A Bartholomeusz
    Department of Experimental Therapeutics, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 109:3470-8. 2007
    ..strongly inhibited colony formation of cells derived from patients with T315I mutant Bcr/Abl-expressing CML in blast crisis. WP1130 suppressed the growth of K562 heterotransplanted tumors as well as both wild-type Bcr/Abl and T315I ..
  93. ncbi Relative importance of apoptosis and cell cycle blockage in the synergistic effect of combined R115777 and imatinib treatment in BCR/ABL-positive cell lines
    Takuji Miyoshi
    Division of Hematology, Jichi Medical School, 3311 1 Yakushiji, Minamikawachi Machi, Kawachi gun, Tochigi 329 0498, Japan
    Biochem Pharmacol 69:1585-94. 2005
    ..Additional treatment for overriding the G1 checkpoint may be required to eradicate leukemia cells, in which the combination induces cell cycle arrest...
  94. ncbi Molecular characterization and sensitivity of STI-571 (imatinib mesylate, Gleevec)-resistant, Bcr-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17-allylamino-17-demethoxygeldanamycin
    Ramadevi Nimmanapalli
    Interdisciplinary Oncology Program, Moffitt Cancer Center, University of South Florida, Tampa 33612, USA
    Cancer Res 62:5761-9. 2002
    ..or PD180970 also induced apoptosis of CD34+ leukemic cells from three patients with chronic myeloid leukemia in blast crisis who had progressive leukemia while receiving Gleevec therapy...
  95. ncbi Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate
    Heather G Jørgensen
    Section of Experimental Haematology, Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Queen Elizabeth Building, Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, Scotland, UK
    Clin Cancer Res 12:626-33. 2006
    ....
  96. ncbi Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up
    Tanja Lahaye
    III Medizinische Klinik Mannheim der Universität Heidelberg, Mannheim, Germany
    Cancer 103:1659-69. 2005
    ..The advent of imatinib has considerably changed the treatment of chronic myeloid leukemia (CML). Early studies demonstrated high rates of hematologic and cytogenetic responses in all phases of the disease after limited observation periods...
  97. ncbi Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure
    Elias Jabbour
    Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 108:1421-3. 2006
    ..Seven patients are alive (6 in CMR) for a median of 19 months. Allo-SCT remains an important salvage option for patients who develop resistance to imatinib through Bcr-Abl mutations...
  98. pmc Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBPalpha
    Giovanna Ferrari-Amorotti
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
    Blood 108:1353-62. 2006
    Chronic phase-to-blast crisis transition in chronic myelogenous leukemia (CML) is associated with differentiation arrest and down-regulation of C/EBPalpha, a transcription factor essential for granulocyte differentiation...
  99. ncbi Sequential mutations causing resistance to both Imatinib Mesylate and Dasatinib in a chronic myeloid leukaemia patient progressing to lymphoid blast crisis
    Fabio Stagno
    Leuk Res 32:673-4. 2008
  100. ncbi Bcr-Abl induces autocrine IGF-1 signaling
    A Lakshmikuttyamma
    Genomic Medicine and Pathobiology Research Group, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
    Oncogene 27:3831-44. 2008
    ..Over time patients become resistant to treatment and progress to blast crisis, an event that is driven by additional genetic and epigenetic aberrations...
  101. ncbi Sudden extramedullary T-lymphoblastic blast crisis in chronic myelogenous leukemia: a nonrandom event associated with imatinib?
    Annette S Kim
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Am J Clin Pathol 129:639-48. 2008
    ..We report 2 cases of sudden BCR/ABL1+ blast crisis in patients with CML who had achieved complete hematologic remission with imatinib therapy but were obligated ..

Research Grants62

  1. ICSBP Function During Myeloid Differentiation
    ELIZABETH ANN EKLUND; Fiscal Year: 2011
    ..common final pathways which is sufficient for myeloproliferation and necessary for susceptibility to myeloid blast crisis. Functional characterization of such a pathway has implications for identifying early markers of disease ..
  2. Molecular Mechanisms of Disease Progression in Myeloid Malignancy
    ELIZABETH ANN EKLUND; Fiscal Year: 2013
    ..Increased [unreadable]catenin activity in CML- CSC/LSC precedes progression to blast crisis (BC), but does not correlate with Wnt expression or CTNNB1 transcription...
  3. Genome instability in leukemia stem cell
    Tomasz Skorski; Fiscal Year: 2010
    ..to ABL kinase inhibitor imatinib mesylate (IM), and to malignant progression of CML- CP to aggressive blast crisis (CML-BC). Resistance to IM is often caused by mutations encoding amino acid substitutions in BCR/ABL kinase...
  4. The role of ICSBP in the pathogenesis of chronic myeloid leukemia
    ELIZABETH ANN EKLUND; Fiscal Year: 2013
    ..Increased ?catenin activity precedes blast crisis (BC) in CML, but does not correlate with Wnt expression or CTNNB1 transcription...
  5. AID-mediated genetic instability in BCR-ABL1-transformed B cell lineage leukemia
    MARKUS MUSCHEN; Fiscal Year: 2013
    ..In a subgroup of patients with CML, however, the disease progresses into B lymphoid blast crisis (CML-LBC), in which treatment responses are as short-lived as in Ph+ ALL...
  6. Proteasome/HDAC Inhibition in Leukemia/MDS; Phase I Trial and Correlative Studies
    Steven Grant; Fiscal Year: 2010
    ..PXD-101) and the proteasome inhibitor (PI) bortezomib in patients with refractory AML, high-risk MDS, CML-blast crisis, and ALL...
  7. GVL Resistance: Immune selection, T cell ignorance and T cell exhaustion
    Warren D Shlomchik; Fiscal Year: 2013
    ..we hoped, the CD8+ TM from miHA-vaccinated donors were potent mediators of GVL against a GVL-resistant model of blast crisis CML (mBC-CML) induced by the retroviral transfer of bcr-abl and NUP98-HOXA9 fusion cDNAs...
  8. Leukemia Stem Cells: Essential Targets for GVL and Mediators of GVL-Resistance
    Warren D Shlomchik; Fiscal Year: 2013
    ..basis for differential susceptibility, even between such closely related leukemias as CP-CML and GVL-resistant blast crisis CML (BC-CML) is unknown...
  9. Role of Setbp1 in leukemic stem cell self-renewal
    Yang Du; Fiscal Year: 2013
    ..BCR/ABL in the generation and maintenance of LSCs in a mouse model of chronic myeloid leukemia (CML) myeloid blast crisis. CML patient samples will also be examined to establish the potential human disease relevance of this ..
  10. "BCR/ABL-PI-3k-ROS pathway induce genomic instability ...."
    Tomasz Skorski; Fiscal Year: 2013
    ..CML usually starts as a relatively benign chronic phase (CML-CP), which progresses to an aggressive disease - blast crisis (CML-BC). Malignant transformation of the disease is associated with accumulation of additional genetic errors...
  11. Role of RNA Binding Proteins in BCR/ABL Leukemogenesis
    Danilo Perrotti; Fiscal Year: 2012
    ..We extensively reported that altered mRNA metabolism is a key feature of blast crisis CML (CML-BC). Indeed, loss-of-function of tumor suppressors (e.g...
  12. c-Myb fusion proteins in Adenoid Cystic Carcinoma
    Timothy P Bender; Fiscal Year: 2012
    ..bone marrow progenitors transduced with a p210BCR/ABL producing virus and extended survival in a model of CML blast crisis. This finding has been extended to transformation of B-lineage progenitors in two models of p190BCR/ABL- ..
  13. Novel SET Antagonists for the Treatment of Chronic Myelogenous Leukemia
    Dale J Christensen; Fiscal Year: 2013
    ..The protracted myelopoliferative chronic phase is followed by a rapidly fatal blast crisis. In CML, a chromosomal translocation leads to production of the Philadelphia Chromosome (Ph1) in which the BCR ..
  14. c-Myb controls survival, proliferation and differentiation during B-lymphopoiesis
    Timothy P Bender; Fiscal Year: 2013
    ..bone marrow progenitors transduced with a p210BCR/ABL producing virus and extended survival in a model of CML blast crisis. This finding has been extended to transformation of B-lineage progenitors in two models of p190BCR/ABL-..
  15. Bypassing Oncogene Addiction: Mechanisms of off-target resistance in CML
    GABRIEL ANTHONY REYES; Fiscal Year: 2013
    ..The natural history of CML involves progression to a more aggressive disease blast crisis phase, where terminal differentiation is impaired, and the disease exhibits features of acute leukemia...
  16. Oncogene Cooperativity in Leukemia Stem Cells
    Craig T Jordan; Fiscal Year: 2013
    ..of "cooperativity response genes" or CRGs in the context of a genetically defined murine model of blast crisis CML...
  17. Targeting the C/EBPalpha-Gfi-pathway in CML stem cells
    Bruno Calabretta; Fiscal Year: 2013
    ..ectopic expression in myeloid leukemia lines and in primary blast cells from chronic myelogenous leukemia (CML)-blast crisis patients induces granulocytic differentiation and inhibits proliferation;this suggests that restoring the ..
  18. Dose-dependent Activation of the MEK/ERK Pathway in Hematopoiesis
    Jing Zhang; Fiscal Year: 2013
    ..determine whether inhibition of MEK1/2 and Jak2 blocks Nras G12D/G12D-mediated MPD and its transformation to a blast crisis. Together, the experiments proposed in these two specific aims will provide insights into the central role of ..
  19. Sequence Based FISH Analysis of Philadelphia Chromosomes
    JOAN KNOLL; Fiscal Year: 2003
    ..These deletions appear to be prognostic for early blast crisis. We hypothesize that these deletions result in hemizygosity of additional genes adjacent to ABLI...
  20. Nostalgia in the WNT signaling pathway; fatty acids, epigenetics and leukemia
    Vincent Sollars; Fiscal Year: 2009
    ..cancer progression, omega fatty acids, and SFRP methylation a mouse BCR-ABL chronic myelogenous leukemia (CML) blast crisis model will be used. In the first Specific Aim, we will determine the effect of high omega 3 canola oil vs...
  21. MOLECULAR EVENTS IN BLAST CRISIS OF CML
    Martin Cline; Fiscal Year: 1993
    Consistent molecular changes associated with the transition of chronic myelocytic leukemia (CML) to blast crisis were not identified until an analysis of the p53 gene in human malignancies revealed a frequent association of alterations of ..
  22. MULTIPLE CHIMERIC TRANSCRIPTS IN THE T(3--21)
    Giuseppina Nucifora; Fiscal Year: 1999
    ..is a recurring abnormality in the malignant cells of patients with chronic myelogenous leukemia in blast crisis and with acute myeloid leukemia primarily following treatment with topoisomerase II inhibitors...
  23. CHROMOSOME ABNORMALITIES AND HUMAN LEUKEMIA AND LYMPHOMA
    Janet Rowley; Fiscal Year: 1999
    ..which is seen in treatment-related acute myelogenous leukemia (t-AML) and in chronic myelogenous leukemia in blast crisis. The gene on chromosome 21 is either the same gene or is a very closely linked gene to that involved in the t(8;..
  24. TLS and TLS Fusion Proteins in Leukemia
    Liu Yang; Fiscal Year: 2005
    ..In acute myelogenous leukemia (AMIL), chronic myelogenous leukemia (CML) in blast crisis, and myelodysplastic syndromes, the TLS (translocation liposarcoma) gene is fused to the ERG (ets-related gene) ..
  25. Src Kinases in Ph+ Lymphoblastic Leukemia
    Shaoguang Li; Fiscal Year: 2009
    ..is highly effective in treating chronic phase CML patients, but is much less effective in treating CML blast crisis and Ph+ B-ALL patients...
  26. NUCLEOSIDE ANALOGS: INTERACTIONS WITH NAD SYNTHESIS
    PRISCILLA SAUNDERS; Fiscal Year: 1993
    ..Clinical studies will also be carried out in concert with a tiazofurin study in patients with leukemia (CML blast crisis)...
  27. PHASE II STUDY OF ARSENIC TRIOXIDE IN LEUKEMIA
    Janice Dutcher; Fiscal Year: 2000
    ..schedule described in the report by Shanghai workers, but patients with all subtypes of myeloid leukemia and blast crisis of chronic myeloid leukemia will be treated. Neurologic toxicity was not described by the Chinese reports...
  28. Gleevec plus novel anti-Bcr-Abl strategies in Leukemias
    Kapil Bhalla; Fiscal Year: 2005
    ..However, these studies need to be extended to patient-derived, CD34+ CML-blast crisis (BC) and Bcr-Abl positive ALL progenitor cells...
  29. Arsenic Based Therapy of Bcr Abl Positive Leukemias
    Kapil Bhalla; Fiscal Year: 2003
    The leukemic clone in virtually all of the patients with chronic myeloid leukemia with blast crisis (CML-BC) and approximately one-third of the adults with acute lymphoblastic leukemia (ALL) expresses the bcr-abl fusion gene encoded p210 ..
  30. Therapeutic Mechanisms in Chronic Myelogenous Leukemia
    George Daley; Fiscal Year: 2005
    ..leukocytosis during the initial chronic phase of CML, but does nothing to alter the inevitable development of blast crisis, an acute leukemia that ultimately proves fatal...
  31. Leukemic transformation by the AML1/MDS1/EVI1 Protein
    Archibald Perkins; Fiscal Year: 2009
    ..The t(3;21) occurs in the setting of therapy-related AML, the blast crisis phase of CML, and de novo AML, and is associated with a particularly poor prognosis...
  32. Phase II and Correlative Studies of Bryo/HiDAC
    Steven Grant; Fiscal Year: 2002
    ..Phase II trial of bryostatin 1 and HiDAC in patients with refractory or relapsed acute leukemia, CML-myeloid blast crisis, or untreated high-risk acute leukemia to define the toxicities and antileukemic activity of this regimen more ..
  33. PI 3K PATHWAY IN BCR/ABL INDUCED LEUKEMIAS
    Tomasz Skorski; Fiscal Year: 2004
    ..the role of PI-3K and its downstream effectors in the malignant progression of CML from chronic phase to blast crisis. For this reason, a murine model will be employed consisting of the BCR/ABL-induced transformation of p53+/+ ..
  34. METABOLISM OF TIAZOFURIN IN HUMAN LEUKEMIA CELLS
    HIREMAGALUR JAYARAM; Fiscal Year: 1993
    Our recent studies on the treatment of twenty-four patients with end stage acute myeloid leukemia and myeloid blast crisis of granulocytic leukemia with tiazofurin revealed that in this poor prognosis group of patients five attained ..
  35. GENE EXPRESSION PROFILE OF PROGRESSION & RESPONSE IN CML
    Jerry Radich; Fiscal Year: 2003
    ..clinically benign state ( chronic phase ), which invariably evolves to an incurable aggressive disease ( blast crisis )...
  36. Bcr-Abl RNA levels to monitor STI571 leukemia therapy
    Richard Press; Fiscal Year: 2004
    ..also induces an initial hematologic response in approximately 50-80% of CML patients with accelerated phase or blast crisis CML, but again these responses are typically only transient...
  37. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2009
    ..Combined, these data should offer significant insights into the biology of and the mechanism of transformation by Bcr-Abl. ..
  38. CBL FUNCTION IN CELLULAR SIGNALING AND TRANSFORMATION
    Brian Druker; Fiscal Year: 2003
    ..Through these studies the investigators should gain a greater understanding of the contribution of tyrosine phosphorylation of Cbl to its function and the role of Cbl in myeloid transformation. ..
  39. Cancer and Kinases
    Brian Druker; Fiscal Year: 2005
    ..By facilitating the development of these drugs, we hope to improve the outcome for patients with cancer as rapidly as possible. ..
  40. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..
  41. Mathematical Models of Programmed CTL Proliferation
    Dominik Wodarz; Fiscal Year: 2009
    ..These are the role of effector molecules (such as perform and IFN-g) for CTL dynamics, and the role of CD4 T cell help. The modeling work will be complemented by experiments with VSV and LCMV infected mice. ..
  42. Farnesyltransferase Inhibitor Therapy for Myelodysplasia
    Razelle Kurzrock; Fiscal Year: 2002
    ....
  43. Role of Redox Dependent Signaling in Leukemia
    Joya Chandra; Fiscal Year: 2010
    ..imatinib mesylate, have dramatically altered the treatment of chronic phase disease, but are less effective in blast crisis and against specific point mutations in BCR/ABL...
  44. Mechanisms of PASG-Mediated Senescence in Hematopoietic Development and Leukemia
    ROBERT JOHN ARCECI; Fiscal Year: 2010
    ..These studies should provide significant information concerning mechanisms of epigenetic patterning and gene expression in normal hematopoiesis and leukemia as well as in risk-group and epigenetically-directed therapies. ..
  45. REGULATION OF IMMUNOGLOBULIN GENE EXPRESSION IN B CELLS
    Ruibao Ren; Fiscal Year: 2003
    ..The rules of combinatorial transcription activation will also allow the design of novel transcription regulatory sequences to direct therapeutic expression of exogenous genes in selected cells. ..
  46. LEUKEMIA ANTIGENS FOLLOWING DONOR LEUKOCYTE INFUSION
    Catherine Wu; Fiscal Year: 2004
    ..abstract_text> ..
  47. Clofarabine: Cytarabine Activation for Leukemia Response
    Stefan Faderl; Fiscal Year: 2004
    ..abstract_text> ..
  48. IDENTIFICATION OF TARGETS OF BCR ABL IN THE LEUKEMOGENIC
    Ruibao Ren; Fiscal Year: 2005
    ..These studies will help to further design rational therapeutic interventions for CML and to understand the mechanisms involved in leukemogenesis in general. ..
  49. c-Kit Activating Mutations and Drug Resistance in AML
    Robert Arceci; Fiscal Year: 2005
    ..These data may also be useful for stratification of patients according to cytokine receptor mutations and subsequent treatment with non-genotoxic therapies that target specific biological pathways. ..
  50. Lyso-PCs activate PMNs and endothelium via PKC
    CHRISTOPHER SILLIMAN; Fiscal Year: 2006
    ..Completion of these specific aims will likely result in targets for in vitro, and possibly clinical, intervention to develop methods to inhibit or to attenuate the effects of these lipids and ultimately make transfusion safer. ..
  51. Updating Chromosome Aberration Simulator (CAS) Software
    Rainer Sachs; Fiscal Year: 2006
    ..An interdisciplinary team has been assembled for this project. The grant would ensure that a computer resource important to the radiation cytogenetics community is kept fully current and readily available. ..
  52. Enhancing Doctor-Patient Communication
    Stephanie Lee; Fiscal Year: 2006
    ..The project works towards the overall goal of enhancing communication, improving patient understanding, and facilitating psychosocial adaptation to life-threatening illness. ..
  53. Regulation of Hematopoiesis by Notch Receptors
    James Griffin; Fiscal Year: 2007
    ..abstract_text> ..
  54. Crosstalk between oncoprotein and chemokine signaling
    Andrzej Ptasznik; Fiscal Year: 2007
    ..The analogous Src kinases-targeted strategy may have application to solid tumors. ..
  55. Measurement & modulation of the mutation rate in humans
    David Araten; Fiscal Year: 2007
    ..These studies will begin to elucidate the relationship between f and cancer risk and provide a highly relevant in vitro parameter with which to evaluate chemoprevention. ..
  56. Examination of imatinib mesylate resistance in CML
    Vivian Oehler; Fiscal Year: 2008
    ..The gene expression pattern of the relapsed sample will be compared with the corresponding diagnostic sample. We hypothesize that the evolution of a previously undetected clone is the mechanism of relapse. ..
  57. GM - CSF - producing tumor cell line as a CML vaccine
    Catherine Wu; Fiscal Year: 2006
    ..The goal of this proposal is to carry out an initial phase I trial using this potentially valuable reagent and thus provide a basis for the continuation and refinement of clinical trials using this reagent. ..
  58. Ras signaling in leukemogenesis
    Ruibao Ren; Fiscal Year: 2010
    ..The ultimate goal of these studies is to identify critical molecular events in Ras leukemogenesis, allowing therapeutic interventions of leukemias involving Ras. ..
  59. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2009
    ..Such crucial proteins may then be exploited as drug targets for the treatment of chronic myeloid leukemia, and further, for other types of cancer. ..
  60. Notch signaling in B cell development and survival
    Warren Pear; Fiscal Year: 2002
    ..abstract_text> ..