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Acute Myeloid Leukemia

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Hematologic Malignancies

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Abstract

Detection of chromosomal abnormalities by cytogenetic analysis is critical in diagnosis and therapeutic decision-making in AML. Detection of t(8;21)(q22;q22.1), inv(16) (p13.1;1q22), t(16;16) (p13.1;q22) or translocations generating PML-RARA t(15;17) fusion transcripts, allow the diagnosis to be made even without the presence of more than or 20% blasts as per WHO classification (2016). These recurrent genetic abnormalities are all associated with a good prognosis. On the other hand, other cytogenetic abnormalities such as complex karyotypes (≥3 cytogenetics abnormalities) without recurring cytogenetic abnormalities are associated with adverse prognosis. A large proportion of AMLs do not show cytogenetic abnormalities and in them identification of CEBPA, NPM1, and FLT3-ITD mutations predict prognosis and response to therapy. Thus, two more entities have been added in cytogenetically positive AML: AML with mutated NPM1 and AML with biallelic CEBPA mutations. AML with RUNX1 mutation and AML with BCR-ABL1 fusion have been added as provisional entities in the WHO classification (2016).

The following 33 case studies include all categories seen in AML: Recurrent cytogenetic abnormalities, AML with myelodysplasia-related changes (AML-MRC), Therapy-related AMLs (t-AML), secondary AMLs (s-AML), and AML-NOS (Annexure).

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References

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2017.

    Google Scholar 

  2. Lagunas-Rangel FA, et al. Acute myeloid leukemia-genetic alterations and their clinical prognosis. Int J Hematol Oncol Stem Cell Res. 2017;11(4):328–39.

    PubMed  PubMed Central  Google Scholar 

  3. Yohe S. Molecular genetic markers in acute myeloid leukemia. J Clin Med. 2015;4:460–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vundinti BR, Kerketta L, Madkaikar M, et al. Three way translocation in a new variant of t(8;21) acute myeloid leukemia involving Xp22. Indian J Cancer. 2008;4(1):30–2.

    Article  Google Scholar 

  5. Mikulasovich M, LeBlanc A, Scalise A, Manwani D, Keyzner A, Najfeld V. Duplication and triplication of der(21)t(8;21)(q22;q22) in acute myeloid leukemia. Cancer Genet Cytogenet. 2009;188:83–7.

    Article  CAS  PubMed  Google Scholar 

  6. Kuykendall A, Duployez N, Boissel N, Lancet JE, Welch JS. Acute myeloid leukemia: the good, the bad. and the ugly. Am Soc Clin Oncol Educ Book. 2018 May;23:555–73.

    Article  Google Scholar 

  7. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Mao L, Wang H, Cheng Y, et al. Occurrence of t(15;17) (q22;q21) and t(9;22) (q34;q11) in a patient with acute promyelocytic leukemia. Leuk Lymphoma. 2009;50(3):466–70. https://doi.org/10.1080/10428190802676728.

    Article  CAS  PubMed  Google Scholar 

  9. Pettijohn EM, et al. Article commentary coexisting of PML-RARa and BCR-ABL in acute promyelocytic leukemia. Leuk Lymphoma. 2013;55(2):238–9.

    Article  PubMed  Google Scholar 

  10. Sun X, He Y, Mao C, et al. BCR-ABL fusion gene detected in acute promyelocytic leukemia: a case study of clinical and laboratory results. Leuk Lymphoma. 2014;55:435–8.

    Article  PubMed  Google Scholar 

  11. Takahashi H, Sakai R, Hattori Y, et al. Biclonal existence t(15;17) and t(9;22) chromosomal abnormalities in acute promyelocytic leukemia. Rinsho Ketsueki. 2011;52:37–40.

    PubMed  Google Scholar 

  12. Sanz MA, Fenaux P, Tallman MS, Estey EH, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European leukemia net. Blood. 2019;133:1630–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Haferlach C, Mecucci C, Schnittger S, et al. AML with mutated NPM carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic and prognostic features. Blood. 2009;114(14):3024–32.

    Article  CAS  PubMed  Google Scholar 

  14. Yoshimoto G, Nagafuji K, Miyamato T, et al. FLT3 mutations in normal karyotype acute myeloid leukemia in first complete remission treated with antologans peripheral blood stem cell transplantation. Bone Marrow Transplant. 2005;36:977–83.

    Article  CAS  PubMed  Google Scholar 

  15. Yung Shih L, Fuang Huang C, Hou Wu J, et al. Heterogeneous patterns of FLT3 Asp 835 mutations in relapsed de novo acute myeloid leukemia. Clin Cancer Res. Feb. 2004;10:1326–32.

    Article  Google Scholar 

  16. Maciejewski J, consultqd cleveland clinic.org. A paradigm shift in conception of aplastic anaemia; 2016.

    Google Scholar 

  17. Takai K, Sananda M, Ketsueki R. Transformation of severe aplastic anemia to myelodysplastic syndrome with monosomy 7 in a patient who achieved transfusion independence after immunosuppressive therapy. Rinsho Ketsueki. 2000;41(4):347–53.

    CAS  PubMed  Google Scholar 

  18. Desangles F. 7/del(7q) in adults. Atlans Genet Cytogenet Oncol Haematol. 1999;3(3):139–40.

    Google Scholar 

  19. Vardiman J, Reichard K. Acute myeloid leukemia with myelodysplasia related changes. Am J Clin Pathol. 2015;144(1):29–43.

    Article  CAS  PubMed  Google Scholar 

  20. Montalban Bravo G, Kanagal-Shamanna R, Sasaki K, et al. Outcome of patients with acute myeloid leukemia (AML) with myelodysplasia related changes (AML-MRC) are dependent on diagnostic criteria and therapy. Blood. 2019;134:1312.

    Article  Google Scholar 

  21. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system (IPSS-R) for myelodysplastic syndrome. Blood. 2012;120:2454–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Anelli L, Pasciolla C, Zagaria A, et al. Monosomal karyotype in myeloid neoplasias: a literature review. Onco Targets Ther. 2017;10:2163–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Patnaik MM, Hanson CA, Hodnefield JM, et al. Monosomal karyotype in myelodysplastic syndromes, with or without monosomy 7 or 5, is prognostically worse than an otherwise complex karyotype. Leukemia. 2011;25(2):266–70.

    Article  CAS  PubMed  Google Scholar 

  24. Solary E, Vainchenker W. Encyclopedia of cancer. 3rd ed. New York: Elsevier; 2019.

    Google Scholar 

  25. Miesner M, Haferlach C, Bacher U. Multilineage dysplasia (MCD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as “AML not otherwise specified” (AML-NOS) or “AML with myelodysplasia-related changes”. Blood. 2010;116(15):2742–51.

    Article  CAS  PubMed  Google Scholar 

  26. Pezeshki A, Podder S, Kamel R, et al. Monosomy 7/del (7q) in inherited bone marrow failure syndromes: a systematic review. Pediatr Blood Cancer. 2017; https://doi.org/10.1002/pbc.26714.

  27. Kayser S, Dohner K, et al. The impact of therapy-related acute myeloid leukemia (AML)an outcome in 2853 adult patients with newly diagnosed AML. Blood. 2017;117(7):2137–45.

    Article  CAS  Google Scholar 

  28. Schoch C, et al. Karyotype is an independent prognostic parameter in therapy related acute myeloid leukemia (t-AML) an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia. 2004;18(1):120–5.

    Article  CAS  PubMed  Google Scholar 

  29. Sarova I, Zemanova Z. Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia. Leuk. Res. 2016;43:51–7. https://doi.org/10.1016/j.leukres.2016.01.001.

    Article  CAS  PubMed  Google Scholar 

  30. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.

    Article  CAS  PubMed  Google Scholar 

  31. Nagy A, Neubauer A. Acute myeloid leukemia with myelodysplasia related changes. Atlas Genet Cytogenet Oncol Haematol. 2017;21(11):404–8.

    Google Scholar 

  32. Huret JL. t(11;19)(q23;p13.1)KMT2A/ELL. Atlas Genet Cytogenet Oncol Hematol. 1997;1(2):104–5.

    Google Scholar 

  33. Moorman AV, Hagemeijer A, Charrin C. The Translocations t(11;19) (q23;p13.1): A cytogenetic and clinical profile of 53 patients. European 11q workshop participants. Leukemia. 1998;12(5):805–10.

    Article  CAS  PubMed  Google Scholar 

  34. Godley LA, Larson RA. Therapy related myeloid leukemia. Semin Oncol. 2008 Aug;35(4):418–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Christiansen DH, Anderson MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype and a poor prognosis. J Clin Oncol. 2001;19(5):1405–13.

    Article  CAS  PubMed  Google Scholar 

  36. Lurlo A, Cattaneo D, Gianelli U. Blast transformation in myeloproliferative neoplasm: risk factors, biological finding and targeted therapeutic options. Int J Mol Sci. 2019;20(8):1839.

    Article  CAS  Google Scholar 

  37. Tefferi A, Guglielmelli P, Larson D, et al. Long term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera and myelofibrosis. Blood. 2014;124(16):2507–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yogarajah M, Tefferi A. Leukemic transformation in myeloproliferative neosplasms. a literature review on risk characteristics and outcome. Mayo Clin Proc. 2017 July;92(7):1118–28.

    CAS  PubMed  Google Scholar 

  39. Hulegardh E, Nilsson C, Lazarevic V, et al. Characterization and prognostic features of secondary acute myeloid leukemia (AML) in a population based setting: a report from the Swedish Acute Leukemia Registry. Am J Hematol. 2015;90:208–14.

    Article  PubMed  Google Scholar 

  40. Ostgard LSG, Medeiros BC, Sengelov H, et al. Epidemiology and clinical significance of secondary and therapy related acute myeloid leukemia: a national population based cohort study. J Clin Oncol. 2015;33(31):3641–9.

    Article  Google Scholar 

  41. Peniket A, Wainscoat J, Side L, et al. Del (9q) AML: clinical and cytological characteristics and prognostic implications. Br J Haematol. 2005 Apr;129(2):210–20.

    Article  PubMed  Google Scholar 

  42. Naarmann-de Vries IS, Sackmann Y, Klein F, Ostareck Lederer A, Ostareck DH, Jost E, Ehninger G, Brummendorf TH, Marx G, Rollig C, Crysandt M. Characterization of acute myeloid leukemia with del(9q) - impact of the genes in the minimally deleted region. Leuk Res. 2019 Jan;76:15–23.

    Article  CAS  PubMed  Google Scholar 

  43. Bhatnagar B, Eisfeld AK, Kohlschmidt J, et al. Clinical and molecular characterization of patients with acute myeloid leukemia and sole trisomies of chromosomes 4,8,11,13 or 21. Leukemia. 28 Aug 2019;34(2):358–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Eisfeld AK, Kohlscjmidt J, Mrozek K, Blachly JS, Nicolet D, Kroll K, et al. Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITD and IDH2. Leukemia. 2016;30:2254–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alseraye FM, Zuo Z, Bueso-Ramos C, Wang S, Medeiros LJ, Lu G. Trisomy 11 as an isolated abnormality in acute myeloid leukemia is associated with unfavorable prognosis but not with an NPM1 or KIT mutation. Int J Clin Exp Pathol. 2011;4:371–7.

    PubMed  PubMed Central  Google Scholar 

  46. Cui W, Bueso Ramos CE, YIN CC, Sun J, Chen S, Muddasani R, Lu G. Trisomy 14 as a sole chromosome abnormality is associated with older age, a heterogenous group of myeloid neoplasms with dysplasia, and a wide spectrum of disease progression. J Biomed Biotechnol. 2010; https://doi.org/10.1155/2010/365318.

  47. Hemsing AL, Hovland R, Tsykunova G, Reikvam H. Trisomy 8 in acute myeloid leukemia. Expert Rev Hematol. 2019; https://doi.org/10.1080/17474086.2019.1657400.

  48. Cuneo A, Cavazzini F, Castoldi GL. Acute megakaryoblastic leukemia AML-M7. Altas Genet Cytogen Oncol Haematol. 2004;8(1):29–30.

    Google Scholar 

  49. Nimer SD, MacGrogan D, Jhanwar S, et al. Chromosome 19 abnormalities are commonly seen in AML-M7. Blood. 2002;100(10):3838–9.

    Article  CAS  PubMed  Google Scholar 

  50. Rucker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119(9):2114–21.

    Article  PubMed  CAS  Google Scholar 

  51. Ruiz Delgado NGJ, Corteza AK, Gazca O, et al. Lineage switch from acute lymphoblastic leukemia to myeloid leukemia. Med Universitaria. 2017;19(74):27–31.

    Article  Google Scholar 

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Authors and Affiliations

  1. Former Senior Advisor and Head Hematopathology, Medanta-The Medicity, New Delhi, India

    Manorama Bhargava

  2. Former Professor and Head Hematology, All India Institute of Medical Sciences and Sir Ganga Ram Hospital, New Delhi, India

    Manorama Bhargava

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  1. Manorama Bhargava
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Annexure

Annexure

  • Case Study 3.1: Acute Myeloid leukemia with t(8;21)(q22;q22.1);RUNX1-RUNX1T1 and KIT Gene Mutation

  • Case Study 3.2: Acute Myeloid leukemia with a variant 3 way translocation t(8;17;21) (q22;q23;22.1);RUNX1-RUNX1T1

  • Case Study 3.3: Acute Myeloid Leukemia, t(8;21)(q22;q22) with rare duplication of der (21)

  • Case Study 3.4: AML with inv(16) (p13;q22)/t(16;16)p(13;q22);CBFB–MYH11

  • Case Study 3.5: Acute Myeloid Leukemia with t(9;11)(p21;q23.3)(KMT2A-MLL3) with Trisomies of Chromosome 8 and 21

  • Case Study 3.6: Acute Promyelocytic leukemia with PML-RARA, t(15;17) with Mutated FLT3-TKD (D835)

  • Case Study 3.7: Acute Promyelocytic leukemia with variant (11;17)(q23;q21.1)(PLZF/RARA)

  • Case Study 3.8: Acute Promyelocytic Leukemia with t(15;17) and t(9;22) Translocations, Trisomy 8 and multiple molecular abnormalities

  • Case Study 3.9: Acute Promyelocytic Leukemia with PML-RARA t(15;17) with mutated FLT3-ITD

  • Case Study 3.10: Acute Myeloid Leukemia with Normal Karyotype, mutated NPM1 and FLT3-ITD

  • Case Study 3.11: Acute Myeloid Leukemia with normal Karyotype and NPM 1 Gene Mutation Mutation

  • Case Study 3.12: Acute Myeloid Leukemia with Normal Karyotype and FL3-ITD Gene Mutation

  • Case Study 3.13: Acute Myeloid Leukemia with t(11;19) and FLT3-ITD Mutation

  • Case Study 3.14: Acute Myeloid Leukemia with Myelodysplasia related changes (AML-MRC) transformed from Aplastic Anaemia

  • Case Study 3.15: Acute Myeloid Leukemia with Myelodysplasia related changes with Monosomy 7

  • Case Study 3.16: Acute Myeloid Leukemia with Myelodysplasia Related Changes with Monosomal Karyotype

  • Case Study 3.17: Acute Myeloid Leukemia (s-AML) from (MDS-EB2) with Myelodysplasia Related Changes with Complex Karyotype

  • Case Study 3.18: Acute Myeloid Leukemia (t-AML) with Myelodysplasia Related Changes with Monosomy 7

  • Case Study 3.19: Acute Myeloid Leukemia with Myelodysplasia Related changes with Complex Karyotype

  • Case Study 3.20: Acute Myeloid Leukemia with Myelodysplasia Related changes (MDS-EB1) with complex Karyotype

  • Case Study 3.21: Acute Myeloid Leukemia (t-AML) with t(11;19)(q23;p13.1) (KMT2A-ELL)

  • Case Study 3.22: Therapy Related Acute Myeloid Leukemia (t-AML) with Hypodiploid Complex Karyotype

  • Case Study 3.23: s-AML with Monocytic Differentiation with der(1) t(1;15)(q11;q13) Evolving from Polycythermia Vera

  • Case Study 3.24: Acute Myeloid Leukemia (s- AML) from Primary Myelofibrosis with Complex Karyotype

  • Case Study 3.25: Acute Megakaryoblastic Leukemia with Isolated deletion 9q

  • Case Study 3.26: Acute Myeloid Leukemia, NOS, with Isolated Trisomy 11

  • Case Study 3.27: Acute Myeloid Leukemia, NOS with Isolated Trisomy 14

  • Case Study 3.28: Acute Myeloid Leukemia, NOS with sole abnormality of Trisomy 8

  • Case Study 3.29: Acute Myeloid Leukemia: AML-M7 (NOS) with Complex Karyotype

  • Case Study 3.30: Acute Myeloid Leukemia with Lineage Switch from ALL with TP53 alterations and Complex Karyotype

  • Case Study 3.31: Acute Myeloid Leukemia with Normal Karyotype and NPM1 mutation on (RT-PCR) with NPM1 and FLT3-ITD mutation on NGS

  • Case Study 3.32: Acute Myeloid Leukemia with t(8;21) and RUNX1-RUNX1T1 Gene Rearrangement on RT-PCR and NGS

  • Case Study 3.33: Acute Myeloid Leukemia with Normal Karyotype and NPM1 mutation on RT-PCR and NGS

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Bhargava, M. (2021). Acute Myeloid Leukemia. In: Hematologic Malignancies. Springer, Singapore. https://doi.org/10.1007/978-981-33-4799-1_3

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  • DOI: https://doi.org/10.1007/978-981-33-4799-1_3

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