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Precision Molecular Pathology of Myeloid Neoplasms pp 99–113Cite as

Chronic Myeloid Leukemia, BCR-ABL1 Positive

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Part of the book series: Molecular Pathology Library ((MPLB,volume 12))

Abstract

BCR-ABL1-positive chronic myeloid leukemia is a clonal neoplasm of abnormal pluripotent bone marrow stem cells. The hallmark cytogenetic abnormality, t(9;22)(q34;q11), produces BCR-ABL1 gene, and that not only plays a critical role in pathogenesis but also provides an excellent target for therapy with various tyrosine kinase inhibitors and a surveillance marker for disease activity and progression. With understanding the molecular pathophysiology and development of tyrosine kinase inhibitors, BCR-ABL1-positive chronic myeloid leukemia turns from a universally fatal disease to a medically manageable disorder. This chapter summarizes the diagnostic criteria for different phases of diseases (chronic, accelerated, and blast), the definitions of different levels of responses (hematologic, cytogenetic, and molecular), and the strategies of monitoring therapeutic responses (conventional karyotyping, FISH, real-time quantitative reverse transcription polymerase chain reaction, and kinase domain mutation detection).

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References

  1. Höglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol. 2015;94:S241–7.

    Article  PubMed  Google Scholar 

  2. Ichimaru M, Tomonaga M, Amenomori T, Matsuo T. Atomic bomb and leukemia. J Radiat Res. 1991;32(Suppl):162–7.

    Article  PubMed  Google Scholar 

  3. Musselman JR, Blair CK, Cerhan JR, Nguyen P, Hirsch B, Ross JA. Risk of adult acute and chronic myeloid leukemia with cigarette smoking and cessation. Cancer Epidemiol. 2013;37(4):410–6.

    Article  PubMed  Google Scholar 

  4. Inbal AA. Retrospective study of patients with chronic myeloid leukemia diagnosed and treated at the Chaim Sheba Medical Center during the years 1966-76. Isr J Med Sci. 1978;14:1259–64.

    CAS  PubMed  Google Scholar 

  5. Kardinal CG, Bateman JR, Weinter J. Chronic granulocytic leukemia: review of 536 cases. Arch Intern Med. 1976;136:305–13.

    Article  CAS  PubMed  Google Scholar 

  6. Hughes TP, Hochhaus A, Branford S, Müller MC, Kaeda JS, Foroni L, Druker BJ, Guilhot F, Larson RA, O'Brien SG, Rudoltz MS, Mone M, Wehrle E, Modur V, Goldman JM, Radich JP, IRIS investigators. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010;116(19):3758–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO classification of tumours of haematopoietic and lymphoid tissue Lyon, France: IARC Press. 2008.

    Google Scholar 

  8. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.

    Article  CAS  PubMed  Google Scholar 

  9. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jennings CD, Foon KA. Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood. 1997;90(8):2863–92.

    CAS  PubMed  Google Scholar 

  11. Béné MC, Nebe T, Bettelheim P, Buldini B, Bumbea H, Kern W, Lacombe F, Lemez P, Marinov I, Matutes E, Maynadié M, Oelschlagel U, Orfao A, Schabath R, Solenthaler M, Tschurtschenthaler G, Vladareanu AM, Zini G, Faure GC, Porwit A. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia. 2011;25:567–74.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  13. Ohsaka A, Shiina S, Kobayashi M, Kudo H, Kawaguchi R. Philadelphia chromosome-positive chronic myeloid leukemia expressing p190(BCR-ABL). Intern Med. 2002;41(12):1183–7.

    Article  PubMed  Google Scholar 

  14. Verma D, Kantarjian HM, Jones D, Luthra R, Borthakur G, Verstovsek S, Rios MB, Cortes J. Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance. Blood. 2009;114:2232–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Song J, Mercer D, Xiaofeng H, Liu H, Li MM. Common leukemia- and lymphoma-associated genetic aberrations in healthy individuals. J Mol Diagn. 2011;13:213–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Roche-Lestienne C, Marceau A, Labis E, Nibourel O, Coiteux V, Guilhot J, Legros L, Nicolini F, Rousselot P, Gardembas M, Helevaut N, Frimat C, Mahon F-X, Guilhotand F, Preudhomme C. Mutation analysis of TET2, IDH1, IDH2 and ASXL1 in chronic myeloid leukemia. Leukemia. 2011;25(10):1661–5.

    Article  CAS  PubMed  Google Scholar 

  17. Schmidt M, Rinke J, Schafer V, Schnittger S, Kohlmann A, Obstfelder E, Kunert C, Ziermann J, Winkelmann N, Eigendorff E, Haferlach T, Haferlach C, Hochhaus A, Ernt T. Molecular-defined clonal evolution in patients with chronic myeloid leukemia independent of the BCR-ABL status. Leukemia. 2014;28:2292–9.

    Article  CAS  PubMed  Google Scholar 

  18. Advani AS, Pendergast AM. Millennium Review. Bcr–Abl variants: biological and clinical aspects. Leuk Res. 2002;26:713–20.

    Article  CAS  PubMed  Google Scholar 

  19. Chereda B, Melo JV. Natural course and biology of CML. Ann Hematol. 2015;94(Suppl 2):S107–21.

    Article  PubMed  Google Scholar 

  20. Kantarjian H, O’Brien S, Jabbour E, Garcia-Manero G, Quintas-Cardama A, Shan J, Rios MB, Ravandi F, Faderl S, Kadia T, Borthakur G, Huang X, Champlin R, Talpaz M, Cortes J. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood. 2012;119(9):1981–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood. 1984;63:789–99.

    CAS  PubMed  Google Scholar 

  22. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst. 1998;90:850–8.

    Article  CAS  PubMed  Google Scholar 

  23. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood. 2011;118:686–92.

    Article  CAS  PubMed  Google Scholar 

  24. Radich JP, Deininger M, Abbound CN, Altman JK, Barta SK, Berman E, Curtin P, DeAngelo DJ, Devine S, Gotlib J, Hagelstrom RT, Hobbs G, Jagasia M, Kantarjian HM, Moore JO, Ontiveros E, Pallera A, Quiery A, Reddy VVB, Rose MG, Shah NP, Smith BD, Snyder DS, Sweet KL, Gregory K, Sundar H. NCCN clinical practice guildlines in oncology (NCCN guilelines) chronic myelogenous leukemia. Version I. 2016. NCCN.org.

  25. Branford S, Fletcher L, Cross NCP, Müller MC, Hochhaus A, Kim D-W, Radich JP, Saglio G, Pane F, Kamel-Reid S, Wang YL, Press RD, Lynch K, Rudzki Z, Goldman JM, Hughes T. Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood. 2008;112:3330–8.

    Article  CAS  PubMed  Google Scholar 

  26. Erbilgin Y, Eskazan AE, Ng OH, Salihoglu A, Elverdi T, Firtina S, Tatonyan SC, Aydin SO, Ar MC, Baslar Z, Sayitoglu M, Ferhanoglu AB, Aydin Y, Ozbek U, Soysal T. Next-generation sequencing of the BCR-ABL1 kinase domain may be beneficial in decision making among chronic myeloid leukemia patients with tyrosine kinase inhibitor resistance. Blood. 2013;122(21):384.

    Google Scholar 

  27. Polakova KM, Kulvait V, Benesova A, Linhartova J, Klamova H, Jaruskova M, de Benedittis C, Haferlach T, Baccarani M, Martinelli G, Stopka T, Ernst T, Hochhaus A, Kohlmann A, Soverini S. Next-generation deep sequencing improves detection of BCR-ABL1 kinase domain mutations emerging under tyrosine kinase inhibitor treatment of chronic myeloid leukemia patients in chronic phase. J Cancer Res Clin Oncol. 2015;141(5):887–99.

    Article  Google Scholar 

  28. Soverini S, Hochhaus A, Nicolini FE, Gruber F, Lange T, Saglio G, Pane F, Martin CM, Ernst T, Rosti G, Porkka K, Baccarani M, Cross NCP, Martinelli G. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011;118(5):1208–15.

    Article  CAS  PubMed  Google Scholar 

  29. Khorashad JS, de Lavallade H, Apperley JF, Milojkovic D, Reid AG, Bua M, Szydlo R, Olavarria E, Kaeda J, Goldman JM, Marin D. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008;26(29):4806–13.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Taichung Veteran General Hospital, Taichung City, Taiwan

    Ren Ching Wang

  2. Department of Pathology, Florida Hospital, University of Central Florida, Orlando, FL, USA

    Chung-Che (Jeff) Chang

Authors
  1. Ren Ching Wang
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  2. Chung-Che (Jeff) Chang
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Correspondence to Chung-Che (Jeff) Chang .

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Editors and Affiliations

  1. Department of Pathology, Florida Hospital, University of Central Florida, Orlando, Florida, USA

    Chung-Che (Jeff) Chang

  2. Department of Pathology, Stanford University, Stanford, California, USA

    Robert S. Ohgami

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Wang, R.C., Chang, CC.(. (2018). Chronic Myeloid Leukemia, BCR-ABL1 Positive. In: Chang, CC., Ohgami, R. (eds) Precision Molecular Pathology of Myeloid Neoplasms. Molecular Pathology Library, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-62146-3_5

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  • DOI: https://doi.org/10.1007/978-3-319-62146-3_5

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-62144-9

  • Online ISBN: 978-3-319-62146-3

  • eBook Packages: MedicineMedicine (R0)

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