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Chronic Myelogenous Leukemia

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Neoplastic Hematopathology

Part of the book series: Contemporary Hematology ((CH))

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Abstract

Chronic myelogenous leukemia, BCR-ABL1+ (CML), is a myeloproliferative neoplasm defined by the presence of the BCR-ABL fusion gene produced by the t(9;22)(q32;q11) cytogenetic abnormality. CML manifests clinically as leukocytosis with circulating immature granulocytic precursors and splenomegaly. When untreated, its natural history is that of inexorable progression to an acute leukemia (blast crisis) after a prolonged chronic phase. The recent development of inhibitors of BCR-ABL tyrosine kinase activity have dramatically altered the clinical course of CML, with long-term remissions in most patients treated early in the course of disease.

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References

  1. Nowell P, Hungerford D. A minute chromosome in human chronic granulocytic leukemia. Science 1960;132:1497-501.

    Google Scholar 

  2. Boveri T. Zur Frage der Entstehung malinger Tumoren. Gustav Fischer, Jena, Germany 1914:64.

    Google Scholar 

  3. Rowley JD. Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet 1973;16:109-12.

    PubMed  CAS  Google Scholar 

  4. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984;36:93-9.

    Article  PubMed  CAS  Google Scholar 

  5. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990;247:824-30.

    Article  PubMed  CAS  Google Scholar 

  6. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA. Cancer J Clin 2004;54:8-29.

    Article  Google Scholar 

  7. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood 2000;96:3343-56.

    PubMed  CAS  Google Scholar 

  8. Bizzozero OJ Jr, Johnson KG, Ciocco A, Kawasaki S, Toyoda S. Radiation-related leukemia in Hiroshima and Nagasaki 1946-1964. II. Ann Intern Med 1967;66:522-30.

    PubMed  Google Scholar 

  9. Corso A, Lazzarino M, Morra E, et al. Chronic myelogenous leukemia and exposure to ionizing radiation-a retrospective study of 443 patients. Ann Hematol 1995;70:79-82.

    Article  PubMed  CAS  Google Scholar 

  10. Aksoy M, Erdem S, DinCol G. Leukemia in shoe-workers exposed chronically to benzene. Blood 1974;44:837-41.

    PubMed  CAS  Google Scholar 

  11. Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med 1999;341:164-72.

    Article  PubMed  CAS  Google Scholar 

  12. Kantarjian HM, Smith TL, McCredie KB, et al. Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival. Blood 1985;66:1326-35.

    PubMed  CAS  Google Scholar 

  13. Aguayo A, Kantarjian H, Manshouri T, et al. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000;96:2240-5.

    PubMed  CAS  Google Scholar 

  14. Hasserjian RP, Boecklin F, Parker S, et al. ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response. Am J Clin Pathol 2002;117:360-7.

    Article  PubMed  CAS  Google Scholar 

  15. Vardiman JW MJ, Baccarani M, Thieke J. Chronic myelogenous leukemia, BCR-ABL1 positive. In: Swerdlow SH CE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, ed. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: International Angency for Research on Cancer (IARC); 2008:32-7

    Google Scholar 

  16. Mark HF, Sokolic RA, Mark Y. Conventional cytogenetics and FISH in the detection of BCR/ABL fusion in chronic myeloid leukemia (CML). Exp Mol Pathol 2006;81:1-7.

    Article  PubMed  CAS  Google Scholar 

  17. Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 1996;88:2375-84.

    PubMed  CAS  Google Scholar 

  18. Laurent E, Talpaz M, Kantarjian H, Kurzrock R. The BCR gene and philadelphia chromosome-positive leukemogenesis. Cancer Res 2001;61:2343-55.

    PubMed  CAS  Google Scholar 

  19. Iwata S, Mizutani S, Nakazawa S, Yata J. Heterogeneity of the breakpoint in the ABL gene in cases with BCR/ABL transcript lacking ABL exon a2. Leukemia 1994;8:1696-702.

    PubMed  CAS  Google Scholar 

  20. Snyder DS, McMahon R, Cohen SR, Slovak ML. Chronic myeloid leukemia with an e13a3 BCR-ABL fusion: benign course responsive to imatinib with an RT-PCR advisory. Am J Hematol 2004;75:92-5.

    Article  PubMed  Google Scholar 

  21. Jones D, Luthra R, Cortes J, et al. BCR-ABL fusion transcript types and levels and their interaction with secondary genetic changes in determining the phenotype of Philadelphia chromosome-positive leukemias. Blood 2008;112:5190-2.

    Article  PubMed  CAS  Google Scholar 

  22. Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 1990;247:1079-82.

    Article  PubMed  CAS  Google Scholar 

  23. Ravandi F, Cortes J, Albitar M, et al. Chronic myelogenous leukaemia with p185(BCR/ABL) expression: characteristics and clinical significance. Br J Haematol 1999;107:581-6.

    Article  PubMed  CAS  Google Scholar 

  24. Lichty BD, Keating A, Callum J, et al. Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. Br J Haematol 1998;103:711-5.

    Article  PubMed  CAS  Google Scholar 

  25. Branford S, Hughes TP, Rudzki Z. Dual transcription of b2a2 and b3a2 BCR-ABL transcripts in chronic myeloid leukaemia is confined to patients with a linked polymorphism within the BCR gene. Br J Haematol 2002;117:875-7.

    Article  PubMed  CAS  Google Scholar 

  26. Luthra R, Sanchez-Vega B, Medeiros LJ. TaqMan RT-PCR assay coupled with capillary electrophoresis for quantification and identification of bcr-abl transcript type. Mod Pathol 2004;17:96-103.

    Article  PubMed  CAS  Google Scholar 

  27. Branford S, Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. Methods Mol Med 2006;125:69-92.

    PubMed  CAS  Google Scholar 

  28. Burmeister T, Reinhardt R. A multiplex PCR for improved detection of typical and atypical BCR-ABL fusion transcripts. Leuk Res 2008;32:579-85.

    Article  PubMed  CAS  Google Scholar 

  29. Schultheis B, Wang L, Clark RE, Melo JV. BCR-ABL with an e6a2 fusion in a CML patient diagnosed in blast crisis. Leukemia 2003;17:2054-5.

    Article  PubMed  CAS  Google Scholar 

  30. Hochhaus A, Reiter A, Skladny H, et al. A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome-negative chronic myelogenous leukemia. Blood 1996;88:2236-40.

    PubMed  CAS  Google Scholar 

  31. Dessars B, El Housni H, Lambert F, Kentos A, Heimann P. Rational use of the EAC real-time quantitative PCR protocol in chronic myelogenous leukemia: report of three false-negative cases at diagnosis. Leukemia 2006;20:886-8.

    Article  PubMed  CAS  Google Scholar 

  32. Taagepera S, McDonald D, Loeb JE, et al. Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci USA 1998;95:7457-62.

    Article  PubMed  CAS  Google Scholar 

  33. Druker BJ, O’Brien SG, Cortes J, Radich J. Chronic myelogenous leukemia. Hematology Am Soc Hematol Educ Program 2002:111-35

    Google Scholar 

  34. Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer 2005;5:172-83.

    Article  PubMed  CAS  Google Scholar 

  35. Gordon MY, Dowding CR, Riley GP, Goldman JM, Greaves MF. Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia. Nature 1987;328:342-4.

    Article  PubMed  CAS  Google Scholar 

  36. Goldman JM, Melo JV. Chronic myeloid leukemia-advances in biology and new approaches to treatment. N Engl J Med 2003;349:1451-64.

    Article  PubMed  CAS  Google Scholar 

  37. Sokal JE, Baccarani M, Russo D, Tura S. Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 1988;25:49-61.

    PubMed  CAS  Google Scholar 

  38. Griesshammer M, Heinze B, Hellmann A, et al. Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients. Ann Hematol 1996;73:225-30.

    Article  PubMed  CAS  Google Scholar 

  39. Kantarjian HM, Deisseroth A, Kurzrock R, Estrov Z, Talpaz M. Chronic myelogenous leukemia: a concise update. Blood 1993;82:691-703.

    PubMed  CAS  Google Scholar 

  40. Xu Y, Dolan MM, Nguyen PL. Diagnostic significance of detecting dysgranulopoiesis in chronic myeloid leukemia. Am J Clin Pathol 2003;120:778-84.

    Article  PubMed  Google Scholar 

  41. Speck B, Bortin MM, Champlin R, et al. Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia. Lancet 1984;1:665-8.

    Article  PubMed  CAS  Google Scholar 

  42. Kantarjian HM, Keating MJ, Smith TL, Talpaz M, McCredie KB. Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia. Am J Med 1990;88:1-8.

    Article  PubMed  CAS  Google Scholar 

  43. Cortes JE, Talpaz M, O’Brien S, et al. Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the World Health Organization proposal. Cancer 2006;106:1306-15.

    Article  PubMed  CAS  Google Scholar 

  44. Quintas-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc 2006;81:973-88.

    Article  PubMed  CAS  Google Scholar 

  45. Gribble SM, Sinclair PB, Grace C, Green AR, Nacheva EP. Comparative analysis of G-banding, chromosome painting, locus-specific fluorescence in situ hybridization, and comparative genomic hybridization in chronic myeloid leukemia blast crisis. Cancer Genet Cytogenet 1999;111:7-17.

    Article  PubMed  CAS  Google Scholar 

  46. Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 2002;107:76-94.

    Article  PubMed  CAS  Google Scholar 

  47. Wu Y, Slovak ML, Snyder DS, Arber DA. Coexistence of inversion 16 and the Philadelphia chromosome in acute and chronic myeloid leukemias: report of six cases and review of literature. Am J Clin Pathol 2006;125:260-6.

    PubMed  Google Scholar 

  48. Merzianu M, Medeiros LJ, Cortes J, et al. inv(16)(p13q22) in chronic myelogenous leukemia in blast phase: a clinicopathologic, cytogenetic, and molecular study of five cases. Am J Clin Pathol 2005;124:807-14.

    Article  PubMed  CAS  Google Scholar 

  49. Melo JV, Barnes DJ. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer 2007;7:441-53.

    Article  PubMed  CAS  Google Scholar 

  50. Salloukh HF, Laneuville P. Increase in mutant frequencies in mice expressing the BCR-ABL activated tyrosine kinase. Leukemia 2000;14:1401-4.

    Article  PubMed  CAS  Google Scholar 

  51. Calabretta B, Perrotti D. The biology of CML blast crisis. Blood 2004;103:4010-22.

    Article  PubMed  CAS  Google Scholar 

  52. Asimakopoulos FA, Shteper PJ, Krichevsky S, et al. ABL1 methylation is a distinct molecular event associated with clonal evolution of chronic myeloid leukemia. Blood 1999;94:2452-60.

    PubMed  CAS  Google Scholar 

  53. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A 2006;103:2794-9.

    Article  PubMed  CAS  Google Scholar 

  54. Jacknow G, Frizzera G, Gajl-Peczalska K, et al. Extramedullary presentation of the blast crisis of chronic myelogenous leukaemia. Br J Haematol 1985;61:225-36.

    Article  PubMed  CAS  Google Scholar 

  55. Saikia T, Advani S, Dasgupta A, et al. Characterisation of blast cells during blastic phase of chronic myeloid leukaemia by immunophenotyping-experience in 60 patients. Leuk Res 1988;12:499-506.

    Article  PubMed  CAS  Google Scholar 

  56. Cortes JE, Talpaz M, Kantarjian H. Chronic myelogenous leukemia: a review. Am J Med 1996;100:555-70.

    Article  PubMed  CAS  Google Scholar 

  57. Khalidi HS, Brynes RK, Medeiros LJ, et al. The immunophenotype of blast transformation of chronic myelogenous leukemia: a high frequency of mixed lineage phenotype in “lymphoid” blasts and A comparison of morphologic, immunophenotypic, and molecular findings. Mod Pathol 1998;11:1211-21.

    PubMed  CAS  Google Scholar 

  58. Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004;351:657-67.

    Article  PubMed  CAS  Google Scholar 

  59. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809-20.

    Article  PubMed  CAS  Google Scholar 

  60. Terre C, Eclache V, Rousselot P, et al. Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia. Leukemia 2004;18:1340-6.

    Article  PubMed  CAS  Google Scholar 

  61. Loriaux M, Deininger M. Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinib. Leuk Lymphoma 2004;45:2197-203.

    Article  PubMed  CAS  Google Scholar 

  62. Jabbour E, Kantarjian HM, Abruzzo LV, et al. Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood 2007;110:2991-5.

    Article  PubMed  CAS  Google Scholar 

  63. Bumm T, Muller C, Al-Ali HK, et al. Emergence of clonal cytogenetic abnormalities in Ph- cells in some CML patients in cytogenetic remission to imatinib but restoration of polyclonal hematopoiesis in the majority. Blood 2003;101:1941-9.

    Article  PubMed  CAS  Google Scholar 

  64. McMullin MF, Humphreys M, Byrne J, Russell NH, Cuthbert RJ, O’Dwyer ME. Chromosomal abnormalities in Ph- cells of patients on imatinib. Blood 2003;102:2700-1. author reply 1.

    Article  PubMed  Google Scholar 

  65. Branford S, Rudzki Z, Walsh S, et al. High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance. Blood 2002;99:3472-5.

    Article  PubMed  CAS  Google Scholar 

  66. Thiele J, Kvasnicka HM, Schmitt-Graeff A, et al. Bone marrow changes in chronic myelogenous leukaemia after long-term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients. Histopathology 2005;46:540-50.

    Article  PubMed  CAS  Google Scholar 

  67. Rosti G, Testoni N, Martinelli G, Baccarani M. The cytogenetic response as a surrogate marker of survival. Semin Hematol 2003;40:56-61.

    PubMed  Google Scholar 

  68. Landstrom AP, Tefferi A. Fluorescent in situ hybridization in the diagnosis, prognosis, and treatment monitoring of chronic myeloid leukemia. Leuk Lymphoma 2006;47:397-402.

    Article  PubMed  CAS  Google Scholar 

  69. Sinclair PB, Nacheva EP, Leversha M, et al. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 2000;95:738-43.

    PubMed  CAS  Google Scholar 

  70. Dewald GW, Wyatt WA, Juneau AL, et al. Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia. Blood 1998;91:3357-65.

    PubMed  CAS  Google Scholar 

  71. Kantarjian H, Schiffer C, Jones D, Cortes J. Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood 2008;111:1774-80.

    Article  PubMed  CAS  Google Scholar 

  72. Branford S, Cross NC, Hochhaus A, et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia. Leukemia 2006;20:1925-30.

    Article  PubMed  CAS  Google Scholar 

  73. Hughes T, Deininger M, Hochhaus A, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108:28-37.

    Article  PubMed  CAS  Google Scholar 

  74. Wang L, Pearson K, Ferguson JE, Clark RE. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol 2003;120:990-9.

    Article  PubMed  CAS  Google Scholar 

  75. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408-17.

    Article  PubMed  CAS  Google Scholar 

  76. Anastasi J, Musvee T, Roulston D, Domer PH, Larson RA, Vardiman JW. Pseudo-Gaucher histiocytes identified up to 1 year after transplantation for CML are BCR/ABL-positive. Leukemia 1998;12:233-7.

    Article  PubMed  CAS  Google Scholar 

  77. Radich JP, Gehly G, Gooley T, et al. Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients. Blood 1995;85:2632-8.

    PubMed  CAS  Google Scholar 

  78. Press RD, Love Z, Tronnes AA, et al. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. Blood 2006;107:4250-6.

    Article  PubMed  CAS  Google Scholar 

  79. Branford S, Rudzki Z, Parkinson I, et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood 2004;104:2926-32.

    Article  PubMed  CAS  Google Scholar 

  80. Cortes J, Talpaz M, O’Brien S, et al. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res 2005;11:3425-32.

    Article  PubMed  CAS  Google Scholar 

  81. Jones D, Kamel-Reid S, Bahler D, et al. Laboratory practice guidelines for detecting and reporting BCR-ABL drug resistance mutations in chronic myelogenous leukemia and acute lymphoblastic leukemia: a report of the Association for Molecular Pathology. J Mol Diagn 2009;11:4-11.

    Article  PubMed  CAS  Google Scholar 

  82. O’Hare T, Eide CA, Deininger MW. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 2007;110:2242-9.

    Article  PubMed  CAS  Google Scholar 

  83. Willis SG, Lange T, Demehri S, et al. High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood 2005;106:2128-37.

    Article  PubMed  CAS  Google Scholar 

  84. Jabbour E, Kantarjian H, Jones D, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia 2006;20:1767-73.

    Article  PubMed  CAS  Google Scholar 

  85. Zhang WW CJ, Yao H, Zhang L, Reddy NG, Jabbour E, Kantarjian HM, Jones D. Predictors of primary imatinib resistance in chronic myeloid leukemia are distinct from those in secondary imatinib resistance. J Clin Oncol 2009;27:3642-3649.

    Google Scholar 

  86. Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 1984;63:789-99.

    PubMed  CAS  Google Scholar 

  87. Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 1998;90:850-8.

    Article  PubMed  CAS  Google Scholar 

  88. Gratwohl A, Hermans J, Niederwieser D, et al. Bone marrow transplantation for chronic myeloid leukemia: long-term results. Chronic Leukemia Working Party of the European Group for Bone Marrow Transplantation. Bone Marrow Transplant 1993;12:509-16.

    PubMed  CAS  Google Scholar 

  89. Buesche G, Hehlmann R, Hecker H, et al. Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia - prospective long-term results from a randomized-controlled trial. Leukemia 2003;17:2444-53.

    Article  PubMed  CAS  Google Scholar 

  90. Buesche G, Ganser A, Schlegelberger B, et al. Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia. Leukemia 2007;21:2420-7.

    Article  PubMed  CAS  Google Scholar 

  91. Sokal JE, Gomez GA, Baccarani M, et al. Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia. Blood 1988;72:294-8.

    PubMed  CAS  Google Scholar 

  92. Farag SS, Ruppert AS, Mrozek K, et al. Prognostic significance of additional cytogenetic abnormalities in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha: a Cancer and Leukemia Group B study. Int J Oncol 2004;25:143-51.

    PubMed  Google Scholar 

  93. Cortes JE, Talpaz M, Giles F, et al. Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood 2003;101:3794-800.

    Article  PubMed  CAS  Google Scholar 

  94. O’Dwyer ME, Mauro MJ, Blasdel C, et al. Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Blood 2004;103:451-5.

    Article  PubMed  CAS  Google Scholar 

  95. Wang Y, Hopwood VL, Hu P, Lennon A, Osterberger J, Glassman A. Determination of secondary chromosomal aberrations of chronic myelocytic leukemia. Cancer Genet Cytogenet 2004;153:53-6.

    Article  PubMed  CAS  Google Scholar 

  96. El-Zimaity MM, Kantarjian H, Talpaz M, et al. Results of imatinib mesylate therapy in chronic myelogenous leukaemia with variant Philadelphia chromosome. Br J Haematol 2004;125:187-95.

    Article  PubMed  CAS  Google Scholar 

  97. Shtalrid M, Talpaz M, Blick M, et al. Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy. J Clin Oncol 1988;6:1569-75.

    PubMed  CAS  Google Scholar 

  98. Lee JJ, Kim HJ, Kim YJ, et al. Imatinib induces a cytogenetic response in blast crisis or interferon failure chronic myeloid leukemia patients with e19a2 BCR-ABL transcripts. Leukemia 2004;18:1539-40.

    Article  PubMed  CAS  Google Scholar 

  99. Verma D, Kantarjian HM, Jones D, et al. Chronic myeloid leukemia (CML) with p190 BCR-ABL: analysis of characteristics, outcomes and prognostic significance. Blood 2009;114:2232-5.

    Google Scholar 

  100. de la Fuente J, Merx K, Steer EJ, et al. ABL-BCR expression does not correlate with deletions on the derivative chromosome 9 or survival in chronic myeloid leukemia. Blood 2001;98:2879-80.

    Article  PubMed  Google Scholar 

  101. Melo JV, Gordon DE, Cross NC, Goldman JM. The ABL-BCR fusion gene is expressed in chronic myeloid leukemia. Blood 1993;81:158-65.

    PubMed  CAS  Google Scholar 

  102. Cohen N, Rozenfeld-Granot G, Hardan I, et al. Subgroup of patients with Philadelphia-positive chronic myelogenous leukemia characterized by a deletion of 9q proximal to ABL gene: expression profiling, resistance to interferon therapy, and poor prognosis. Cancer Genet Cytogenet 2001;128:114-9.

    Article  PubMed  CAS  Google Scholar 

  103. Huntly BJ, Reid AG, Bench AJ, et al. Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. Blood 2001;98:1732-8.

    Article  PubMed  CAS  Google Scholar 

  104. Huntly BJ, Guilhot F, Reid AG, et al. Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions. Blood 2003;102:2205-12.

    Article  PubMed  CAS  Google Scholar 

  105. Yoong Y, VanDeWalker TJ, Carlson RO, Dewald GW, Tefferi A. Clinical correlates of submicroscopic deletions involving the ABL-BCR translocation region in chronic myeloid leukemia. Eur J Haematol 2005;74:124-7.

    Article  PubMed  CAS  Google Scholar 

  106. Quintas-Cardama A, Kantarjian H, Talpaz M, et al. Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia. Blood 2005;105:2281-6.

    Article  PubMed  CAS  Google Scholar 

  107. Kreil S, Pfirrmann M, Haferlach C, et al. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia. Blood 2007;110:1283-90.

    Article  PubMed  CAS  Google Scholar 

  108. Yong AS, Szydlo RM, Goldman JM, Apperley JF, Melo JV. Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML. Blood 2006;107:205-12.

    Article  PubMed  CAS  Google Scholar 

  109. Martin-Henao GA, Quiroga R, Sureda A, Garcia J. CD7 expression on CD34+ cells from chronic myeloid leukaemia in chronic phase. Am J Hematol 1999;61:178-86.

    Article  PubMed  CAS  Google Scholar 

  110. Kosugi N, Ebihara Y, Nakahata T, Saisho H, Asano S, Tojo A. CD34+CD7+ leukemic progenitor cells may be involved in maintenance and clonal evolution of chronic myeloid leukemia. Clin Cancer Res 2005;11:505-11.

    PubMed  CAS  Google Scholar 

  111. Kaneta Y, Kagami Y, Katagiri T, et al. Prediction of sensitivity to STI571 among chronic myeloid leukemia patients by genome-wide cDNA microarray analysis. Jpn J Cancer Res 2002;93:849-56.

    Article  PubMed  CAS  Google Scholar 

  112. Ohno R, Nakamura Y. Prediction of response to imatinib by cDNA microarray analysis. Semin Hematol 2003;40:42-9.

    Article  PubMed  CAS  Google Scholar 

  113. McLean LA, Gathmann I, Capdeville R, Polymeropoulos MH, Dressman M. Pharmacogenomic analysis of cytogenetic response in chronic myeloid leukemia patients treated with imatinib. Clin Cancer Res 2004;10:155-65.

    Article  PubMed  CAS  Google Scholar 

  114. Rosner F, Schreiber ZR, Parise F. Leukocyte alkaline phosphatase. Fluctuations with disease status in chronic granulocytic leukemia. Arch Intern Med 1972;130:892-4.

    Article  PubMed  CAS  Google Scholar 

  115. Pane F, Frigeri F, Sindona M, et al. Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction). Blood 1996;88:2410-4.

    PubMed  CAS  Google Scholar 

  116. Soupir CP, Vergilio JA, Dal Cin P, et al. Philadelphia chromosome-positive acute myeloid leukemia: a rare aggressive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis. Am J Clin Pathol 2007;127:642-50.

    Article  PubMed  Google Scholar 

  117. Deininger M. Resistance and relapse with imatinib in CML: causes and consequences. J Natl Compr Canc Netw 2008;6(Suppl 2):S11-21.

    Google Scholar 

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  1. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Robert P. Hasserjian

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  1. Robert P. Hasserjian
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Correspondence to Robert P. Hasserjian .

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  1. M.D. Anderson Cancer Center, The University of Texas, Holcombe Blvd. 1515 , Houston, 77030, U.S.A.

    Dan Jones

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Hasserjian, R.P. (2010). Chronic Myelogenous Leukemia. In: Jones, D. (eds) Neoplastic Hematopathology. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-384-8_10

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  • DOI: https://doi.org/10.1007/978-1-60761-384-8_10

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