Advertisement

Current Hematologic Malignancy Reports

, Volume 13, Issue 6, pp 435–445 | Cite as

Chronic Myeloid Leukemia: Beyond BCR-ABL1

  • Ting ZhouEmail author
  • L. Jeffrey Medeiros
  • Shimin HuEmail author
Molecular Testing and Diagnostics (J Khoury, Section Editor)
  • 315 Downloads
Part of the following topical collections:
  1. Topical Collection on Molecular Testing and Diagnostics

Abstract

Purpose of review

In this review, we emphasize up-to-date practical cytogenetic and molecular aspects of chronic myeloid leukemia (CML) and summarize current knowledge on tyrosine kinase inhibitor (TKI) resistance and treatment response monitoring of CML.

Recent findings

The introduction of TKIs has changed the natural course of CML and markedly improved patient survival. Over the past decades, many research efforts were devoted to elucidating the leukemogenic mechanisms of BCR-ABL1 and developing novel TKIs. More recent studies have attempted to answer new questions that have emerged in the TKI era, such as the cytogenetic and molecular bases of treatment failure and disease progression, the clinical impact of genetic aberrations in Philadelphia chromosome (Ph)-positive and Ph-negative cells, and the biological significance of Ph secondarily acquired during therapy of other hematological neoplasms.

Summary

Recent progresses in the understanding of the cytogenetic and molecular mechanisms underlying therapeutic failure and disease progression have improved the risk stratification of CML and will be helpful in the design of novel therapeutic strategies.

Keywords

Chronic myeloid leukemia Philadelphia chromosome BCR-ABL1 Tyrosine kinase inhibitor Additional chromosomal abnormality TKI resistance 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer. 2005;5(3):172–83.PubMedGoogle Scholar
  2. 2.
    Ahmed W, Van Etten RA. Alternative approaches to eradicating the malignant clone in chronic myeloid leukemia: tyrosine-kinase inhibitor combinations and beyond. Hematology Am Soc Hematol Educ Program. 2013;2013:189–200.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Cilloni D, Saglio G. Molecular pathways: BCR-ABL. Clin Cancer Res. 2012;18(4):930–7.PubMedGoogle Scholar
  4. 4.
    Goh HG, Hwang JY, Kim SH, Lee YH, Kim YL, Kim DW. Comprehensive analysis of BCR-ABL transcript types in Korean CML patients using a newly developed multiplex RT-PCR. Transl Res. 2006;148(5):249–56.PubMedGoogle Scholar
  5. 5.
    Arun AK, Senthamizhselvi A, Mani S, Vinodhini K, Janet NB, Lakshmi KM, et al. Frequency of rare BCR-ABL1 fusion transcripts in chronic myeloid leukemia patients. Int J Lab Hematol. 2017;39(3):235–42.PubMedGoogle Scholar
  6. 6.
    Melo JV, Barnes DJ. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer. 2007;7(6):441–53.PubMedGoogle Scholar
  7. 7.
    Gong Z, Medeiros LJ, Cortes JE, Zheng L, Khoury JD, Wang W, et al. Clinical and prognostic significance of e1a2 BCR-ABL1 transcript subtype in chronic myeloid leukemia. Blood Cancer J. 2017;7(7):e583.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Li S, Ilaria RL Jr, Million RP, Daley GQ, van Etten R. The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J Exp Med. 1999;189(9):1399–412.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Castor A, Nilsson L, Åstrand-Grundström I, Buitenhuis M, Ramirez C, Anderson K, et al. Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med. 2005;11(6):630–7.PubMedGoogle Scholar
  10. 10.
    Lugo TG, Witte ON. The BCR-ABL oncogene transforms Rat-1 cells and cooperates with v-myc. Mol Cell Biol. 1989;9(3):1263–70.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Kelliher M, Knott A, McLaughlin J, Witte ON, Rosenberg N. Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol. 1991;11(9):4710–6.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Voncken JW, Kaartinen V, Pattengale PK, Germeraad WT, Groffen J, Heisterkamp N. BCR/ABL P210 and P190 cause distinct leukemia in transgenic mice. Blood. 1995;86(12):4603–11.PubMedGoogle Scholar
  13. 13.
    Reckel S, Hamelin R, Georgeon S, Armand F, Jolliet Q, Chiappe D, et al. Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics. Leukemia. 2017;31(7):1502–12.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Danial NN, Pernis A, Rothman PB. Jak-STAT signaling induced by the v-abl oncogene. Science. 1995;269(5232):1875–7.PubMedGoogle Scholar
  15. 15.
    Ilaria RL Jr, van Etten RA. P210 and P190BCR/ABL induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chem. 1996;271(49):31704–10.PubMedGoogle Scholar
  16. 16.
    Kaplan MH, Schindler U, Smiley ST, Grusby MJ. Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity. 1996;4(3):313–9.PubMedGoogle Scholar
  17. 17.
    Telegeev GD, Dubrovska AN, Nadgorna VA, Dybkov MV, Zavelevich MP, Maliuta SS, et al. Immunocytochemical study of Bcr and Bcr-Abl localization in K562 cells. Exp Oncol. 2010;32(2):81–3.PubMedGoogle Scholar
  18. 18.
    Heisterkamp N, Voncken JW, Senadheera D, Gonzalez-Gomez I, Reichert A, Haataja L, et al. Reduced oncogenicity of p190 Bcr/Abl F-actin-binding domain mutants. Blood. 2000;96(6):2226–32.PubMedGoogle Scholar
  19. 19.
    Hantschel O, Wiesner S, Güttler T, Mackereth CD, Rix LL, Mikes Z, et al. Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl. Mol Cell. 2005;19(4):461–73.PubMedGoogle Scholar
  20. 20.
    Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel). 2017;9(5):52.Google Scholar
  21. 21.
    Birge RB, et al. Crk and CrkL adaptor proteins: networks for physiological and pathological signaling. Cell Commun Signal. 2009;7:13.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Varticovski L, Daley GQ, Jackson P, Baltimore D, Cantley LC. Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants. Mol Cell Biol. 1991;11(2):1107–13.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Jain SK, Susa M, Keeler ML, Carlesso N, Druker B, Varticovski L. PI 3-kinase activation in BCR/abl-transformed hematopoietic cells does not require interaction of p85 SH2 domains with p210 BCR/abl. Blood. 1996;88(5):1542–50.PubMedGoogle Scholar
  24. 24.
    Shuai K, Halpern J, ten Hoeve J, Rao X, Sawyers CL. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene. 1996;13(2):247–54.PubMedGoogle Scholar
  25. 25.
    Gaymes TJ, Mufti GJ, Rassool FV. Myeloid leukemias have increased activity of the nonhomologous end-joining pathway and concomitant DNA misrepair that is dependent on the Ku70/86 heterodimer. Cancer Res. 2002;62(10):2791–7.PubMedGoogle Scholar
  26. 26.
    Hoover RR, Gerlach MJ, Koh EY, Daley GQ. Cooperative and redundant effects of STAT5 and Ras signaling in BCR/ABL transformed hematopoietic cells. Oncogene. 2001;20(41):5826–35.PubMedGoogle Scholar
  27. 27.
    Nowicki MO, Falinski R, Koptyra M, Slupianek A, Stoklosa T, Gloc E, et al. BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks. Blood. 2004;104(12):3746–53.PubMedGoogle Scholar
  28. 28.
    Albajar M, Gomez-Casares MT, Llorca J, Mauleon I, Vaque JP, Acosta JC, et al. MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib. Mol Cancer Res. 2011;9(5):564–76.PubMedGoogle Scholar
  29. 29.
    •• Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol. 2002;107(2):76–94 Comprehensive and elegant review of cytogenetic changes in CML in pre-TKI era. PubMedGoogle Scholar
  30. 30.
    Mu Q, Ma Q, Wang Y, Chen Z, Tong X, Chen FF, et al. Cytogenetic profile of 1,863 Ph/BCR-ABL-positive chronic myelogenous leukemia patients from the Chinese population. Ann Hematol. 2012;91(7):1065–72.PubMedGoogle Scholar
  31. 31.
    Calabretta B, Perrotti D. The biology of CML blast crisis. Blood. 2004;103(11):4010–22.PubMedGoogle Scholar
  32. 32.
    •• Baccarani M, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84 Updated recommendations for treatment and monitoring of CML. PubMedPubMedCentralGoogle Scholar
  33. 33.
    Fioretos T. Chronic myeloid leukemia. In: Heim S, Mitelman F, editors. Cancer cytogenetics. Hoboken: Wiley; 2016. p. 153–74.Google Scholar
  34. 34.
    Soverini S, Branford S, Nicolini FE, Talpaz M, Deininger MW, Martinelli G, et al. Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia. Leuk Res. 2014;38(1):10–20.PubMedGoogle Scholar
  35. 35.
    Hanfstein B, Muller MC, Hochhaus A. Response-related predictors of survival in CML. Ann Hematol. 2015;94(Suppl 2):S227–39.PubMedGoogle Scholar
  36. 36.
    Hehlmann R, Hasford J, Pfirrmann M, Lauseker M, Saußele S, Hochhaus A, et al. Reply to H. Kantarjian et al. J Clin Oncol. 2014;32(27):3078–9.PubMedGoogle Scholar
  37. 37.
    Chen Z, Medeiros LJ, Kantajian HM, Zheng L, Gong Z, Patel KP, et al. Differential depth of treatment response required for optimal outcome in patients with blast phase versus chronic phase of chronic myeloid leukemia. Blood Cancer J. 2017;7(2):e521.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Chaitanya PK, Kumar KA, Stalin B, Sadashivudu G, Srinivas ML. The role of mutation testing in patients with chronic myeloid leukemia in chronic phase after imatinib failure and their outcomes after treatment modification: single-institutional experience over 13 years. Indian J Med Paediatr Oncol. 2017;38(3):328–33.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Quintas-Cardama A, Kantarjian HM, Cortes JE. Mechanisms of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control. 2009;16(2):122–31.PubMedGoogle Scholar
  40. 40.
    Jabbour E, Kantarjian H, Jones D, Talpaz M, Bekele N, O'Brien S, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006;20(10):1767–73.PubMedGoogle Scholar
  41. 41.
    Soverini S, Colarossi S, Gnani A, Rosti G, Castagnetti F, Poerio A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12(24):7374–9.PubMedGoogle Scholar
  42. 42.
    O'Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 2012;12(8):513–26.PubMedGoogle Scholar
  43. 43.
    Apperley JF. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8(11):1018–29.PubMedGoogle Scholar
  44. 44.
    Sherbenou DW, Hantschel O, Kaupe I, Willis S, Bumm T, Turaga LP, et al. BCR-ABL SH3-SH2 domain mutations in chronic myeloid leukemia patients on imatinib. Blood. 2010;116(17):3278–85.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Barnes DJ, Palaiologou D, Panousopoulou E, Schultheis B, Yong ASM, Wong A, et al. Bcr-Abl expression levels determine the rate of development of resistance to imatinib mesylate in chronic myeloid leukemia. Cancer Res. 2005;65(19):8912–9.PubMedGoogle Scholar
  46. 46.
    Jiang X, Zhao Y, Smith C, Gasparetto M, Turhan A, Eaves A, et al. Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia. 2007;21(5):926–35.PubMedGoogle Scholar
  47. 47.
    Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004;104(12):3739–45.PubMedGoogle Scholar
  48. 48.
    Hamilton A, Helgason GV, Schemionek M, Zhang B, Myssina S, Allan EK, et al. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival. Blood. 2012;119(6):1501–10.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Perl A, Carroll M. BCR-ABL kinase is dead; long live the CML stem cell. J Clin Invest. 2011;121(1):22–5.PubMedGoogle Scholar
  50. 50.
    Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 2011;121(1):396–409.PubMedGoogle Scholar
  51. 51.
    Wang W, Cortes JE, Lin P, Beaty MW, Ai D, Amin HM, et al. Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors. Blood. 2015;126(14):1699–706.PubMedPubMedCentralGoogle Scholar
  52. 52.
    •• Chen Z, et al. Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Leukemia. 2017;31(3):585–92 Demonstration of changes in ACA landscape, prognostic impact of ACAs, and relationship between ACAs in CML-BP in TKI era. PubMedGoogle Scholar
  53. 53.
    Wu J, Meng F, Kong LY, Peng Z, Ying Y, Bornmann WG, et al. Association between imatinib-resistant BCR-ABL mutation-negative leukemia and persistent activation of LYN kinase. J Natl Cancer Inst. 2008;100(13):926–39.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Quentmeier H, Eberth S, Romani J, Zaborski M, Drexler HG. BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance. J Hematol Oncol. 2011;4:6.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T, Decosterd LA. Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011;117(8):e75–87.PubMedGoogle Scholar
  56. 56.
    White DL, Saunders VA, Dang P, Engler J, Venables A, Zrim S, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood. 2007;110(12):4064–72.PubMedGoogle Scholar
  57. 57.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Switzerland: WHO Press; 2017.Google Scholar
  58. 58.
    • Wang W, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood. 2016;127(22):2742–50 Stratification of CML patients based on ACA-associated patient survival in TKI era. PubMedPubMedCentralGoogle Scholar
  59. 59.
    •• Gong Z, et al. Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy. Blood Adv. 2017;1(26):2541–52 Four-tier stratification of CML based on ACA-associated risk of blastic transformation. PubMedPubMedCentralGoogle Scholar
  60. 60.
    Johansson B, Fioretos T, Billström R, Mitelman F. Aberrant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha. Leukemia. 1996;10(7):1134–8.PubMedGoogle Scholar
  61. 61.
    Mitelman F, Johansson B, Mertens F. https://cgap.nci.nih.gov/Chromosomes/Mitelman. 2001. Accessed 1 Aug 2018.
  62. 62.
    Gaiger A, Henn T, Hörth E, Geissler K, Mitterbauer G, Maier-Dobersberger T, et al. Increase of BCR-ABL chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. Blood. 1995;86(6):2371–8.PubMedGoogle Scholar
  63. 63.
    Guo JQ, Wang JY, Arlinghaus RB. Detection of BCR-ABL proteins in blood cells of benign phase chronic myelogenous leukemia patients. Cancer Res. 1991;51(11):3048–51.PubMedGoogle Scholar
  64. 64.
    Barnes DJ, Schultheis B, Adedeji S, Melo JV. Dose-dependent effects of Bcr-Abl in cell line models of different stages of chronic myeloid leukemia. Oncogene. 2005;24(42):6432–40.PubMedGoogle Scholar
  65. 65.
    Cambier N, Chopra R, Strasser A, Metcalf D, Elefanty AG. BCR-ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose-dependent manner. Oncogene. 1998;16(3):335–48.PubMedGoogle Scholar
  66. 66.
    Grossmann V, Kohlmann A, Zenger M, Schindela S, Eder C, Weissmann S, et al. A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases. Leukemia. 2011;25(3):557–60.PubMedGoogle Scholar
  67. 67.
    Notari M, Neviani P, Santhanam R, Blaser BW, Chang JS, Galietta A, et al. A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation. Blood. 2006;107(6):2507–16.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Jennings BA, Mills KI. c-myc locus amplification and the acquisition of trisomy 8 in the evolution of chronic myeloid leukaemia. Leuk Res. 1998;22(10):899–903.PubMedGoogle Scholar
  69. 69.
    Jamieson CH, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351(7):657–67.PubMedGoogle Scholar
  70. 70.
    Radich JP, Dai H, Mao M, Oehler V, Schelter J, Druker B, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A. 2006;103(8):2794–9.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Zhang SJ, Ma LY, Huang QH, Li G, Gu BW, Gao XD, et al. Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci U S A. 2008;105(6):2076–81.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Hehlmann R. How I treat CML blast crisis. Blood. 2012;120(4):737–47.PubMedGoogle Scholar
  73. 73.
    Sill H, Goldman JM, Cross NC. Homozygous deletions of the p16 tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia. Blood. 1995;85(8):2013–6.PubMedGoogle Scholar
  74. 74.
    Mullighan CG, Miller CB, Radtke I, Phillips LA, Dalton J, Ma J, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453(7191):110–4.PubMedGoogle Scholar
  75. 75.
    Yin Y, Li J, Yan W, Cheng Z, Sun N, Zhang G. CEBPA mutation in a case of chronic myeloid leukemia presenting in myeloid blast crisis. Leuk Lymphoma. 2017;58(3):708–10.PubMedGoogle Scholar
  76. 76.
    Dash AB, Williams IR, Kutok JL, Tomasson MH, Anastasiadou E, Lindahl K, et al. A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proc Natl Acad Sci U S A. 2002;99(11):7622–7.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Nucifora G, Birn DJ, Espinosa R 3rd, Erickson P, LeBeau M, Roulston D, et al. Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. Blood. 1993;81(10):2728–34.PubMedGoogle Scholar
  78. 78.
    Di Giacomo D, et al. Blast crisis Ph+ chronic myeloid leukemia with NUP98/HOXA13 up-regulating MSI2. Mol Cytogenet. 2014;7:42.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Shteper PJ, Ben-Yehuda D. Molecular evolution of chronic myeloid leukaemia. Semin Cancer Biol. 2001;11(4):313–23.PubMedGoogle Scholar
  80. 80.
    Heller G, Topakian T, Altenberger C, Cerny-Reiterer S, Herndlhofer S, Ziegler B, et al. Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia. Leukemia. 2016;30(9):1861–8.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Jelinek J, Gharibyan V, Estecio MRH, Kondo K, He R, Chung W, et al. Aberrant DNA methylation is associated with disease progression, resistance to imatinib and shortened survival in chronic myelogenous leukemia. PLoS One. 2011;6(7):e22110.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Issa JP, Kantarjian H, Mohan A, O'Brien S, Cortes J, Pierce S, et al. Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of prognostic significance. Blood. 1999;93(6):2075–80.PubMedGoogle Scholar
  83. 83.
    Kim T, Tyndel MS, Kim HJ, Ahn JS, Choi SH, Park HJ, et al. Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy. Blood. 2017;129(1):38–47.PubMedGoogle Scholar
  84. 84.
    Terre C, 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(8):1340–6.PubMedGoogle Scholar
  85. 85.
    O'Dwyer ME, Gatter KM, Loriaux M, Druker BJ, Olson SB, Magenis RE, et al. Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate. Leukemia. 2003;17(3):481–7.PubMedGoogle Scholar
  86. 86.
    Jabbour E, Kantarjian HM, Abruzzo LV, O'Brien S, Garcia-Manero G, Verstovsek S, 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(8):2991–5.PubMedGoogle Scholar
  87. 87.
    Medina J, Kantarjian H, Talpaz M, O'Brien S, Garcia-Manero G, Giles F, et al. Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Cancer. 2003;98(9):1905–11.PubMedGoogle Scholar
  88. 88.
    Deininger MW, Cortes J, Paquette R, Park B, Hochhaus A, Baccarani M, et al. The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells. Cancer. 2007;110(7):1509–19.PubMedGoogle Scholar
  89. 89.
    Kovitz C, Kantarjian H, Garcia-Manero G, Abruzzo LV, Cortes J. Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate therapy for chronic myeloid leukemia. Blood. 2006;108(8):2811–3.PubMedGoogle Scholar
  90. 90.
    Groves MJ, Sales M, Baker L, Griffiths M, Pratt N, Tauro S. Factors influencing a second myeloid malignancy in patients with Philadelphia-negative −7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia. Cancer Genet. 2011;204(1):39–44.PubMedGoogle Scholar
  91. 91.
    • Kurt H, Zheng L, Kantarjian HM, Tang G, Ravandi-Kashani F, Garcia-Manero G, et al. Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome. Mod Pathol. 2018. Comprehensive study of emergence of secondary Ph and its significance.;31:1141–54.PubMedGoogle Scholar
  92. 92.
    Chen Z, Wang W, Verstovsek S, Cortes JE, Medeiros LJ, Hu S. Chronic myelogenous leukemia in patients with MPL or JAK2 mutation-positive myeloproliferative neoplasm. Int J Lab Hematol. 2015;37(6):e150–2.PubMedGoogle Scholar
  93. 93.
    Soderquist CR, Ewalt MD, Czuchlewski DR, Geyer JT, Rogers HJ, Hsi ED, et al. Myeloproliferative neoplasms with concurrent BCR-ABL1 translocation and JAK2 V617F mutation: a multi-institutional study from the bone marrow pathology group. Mod Pathol. 2018;31(5):690–704.PubMedGoogle Scholar
  94. 94.
    Pingali SR, et al. Emergence of chronic myelogenous leukemia from a background of myeloproliferative disorder: JAK2V617F as a potential risk factor for BCR-ABL translocation. Clin Lymphoma Myeloma. 2009;9(5):E25–9.PubMedGoogle Scholar
  95. 95.
    Mirza I, Frantz C, Clarke G, Voth AJ, Turner R. Transformation of polycythemia vera to chronic myelogenous leukemia. Arch Pathol Lab Med. 2007;131(11):1719–24.PubMedGoogle Scholar
  96. 96.
    Shimizu H, Yokohama A, Hatsumi N, Takada S, Handa H, Sakura T, et al. Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib era. Eur J Haematol. 2014;93(4):297–301.PubMedGoogle Scholar
  97. 97.
    de Franca Azevedo I, et al. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia. Rev Bras Hematol Hemoter. 2014;36(5):351–5.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Jaso J, Thomas DA, Cunningham K, Jorgensen JL, Kantarjian HM, Medeiros LJ, et al. Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B-lymphoblastic leukemia in the era of tyrosine kinase inhibitors. Cancer. 2011;117(17):4009–17.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Verrma SP, Dutta TK, Vinod KV, Dubashi B, Ariga KK. Philadelphia chromosome positive pre-T cell acute lymphoblastic leukemia: a rare case report and short review. Indian J Hematol Blood Transfus. 2014;30(Suppl 1):177–9.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Soupir CP, Vergilio JA, Cin PD, Muzikansky A, Kantarjian H, Jones D, 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(4):642–50.PubMedGoogle Scholar
  101. 101.
    Konopleva M, et al. Molecular biology and cytogenetics of chronic myeloid leukemia. In: P.H. Wiemik, J.P. Dutcher, and M.A. Gertz, eds. Neoplastic Disease of the Blood. Springer. 2018:29-47.Google Scholar
  102. 102.
    Reboursiere E, Chantepie S, Gac AC, Reman O. Rare but authentic Philadelphia-positive acute myeloblastic leukemia: two case reports and a literature review of characteristics, treatment and outcome. Hematol Oncol Stem Cell Ther. 2015;8(1):28–33.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology & ImmunologyBaylor College of MedicineHoustonUSA
  2. 2.Department of HematopathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations