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Acute Myeloid Neoplasms

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Genomic Medicine

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Abstract

Genetic profiling has been central to the diagnosis and taxonomy of hematopoietic neoplasms for over a decade. Acute myeloid leukemias are a heterogeneous subgroup of myeloid neoplasms with an aggressive clinical course, and the majority of these cases are defined by their underlying genetics. Cytogenetic evaluation retains a primary role in the evaluation and subclassification of these entities, but incorporation of molecular sequencing data has quickly become increasingly important for diagnosis, prognosis, and clinical management.

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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 (Revised 4th edition). Lyon: IARC; 2017.

    Google Scholar 

  2. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059–74.

    Article  CAS  Google Scholar 

  3. Devillier R, Gelsi-Boyer V, Brecqueville M, Carbuccia N, Murati A, Vey N, et al. Acute myeloid leukemia with myelodysplasia-related changes are characterized by a specific molecular pattern with high frequency of ASXL1 mutations. Am J Hematol. 2012;87:659–62.

    Article  CAS  PubMed  Google Scholar 

  4. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354–65.

    Article  CAS  PubMed  Google Scholar 

  5. Byrd JC, Mrózek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100(13):4325–36.

    Article  CAS  PubMed  Google Scholar 

  6. Paschka P, Du J, Schlenk RF, Gaidzik VI, Bullinger L, Corbacioglu A, et al. Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood. 2013;121(1):170–7.

    Article  CAS  PubMed  Google Scholar 

  7. Itzykson R, Duployez N, Fasan A, Decool G, Marceau-Renaut A, Meggendorfer M, et al. Clonal interference of signaling mutations holds prognostic relevance in core binding factor acute myeloid leukemia. Blood. 2018;132:187–96. Epub ahead of print. PMID: 29692343

    Article  CAS  PubMed  Google Scholar 

  8. Duployez N, Marceau-Renaut A, Boissel N, Petit A, Bucci M, Geffroy S, et al. Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood. 2016;127(20):2451–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Micol JB, Duployez N, Boissel N, Petit A, Geffroy S, Nibourel O, et al. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations. Blood. 2014;124(9):1445–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yin JA, O’Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood. 2012;120(14):2826–35.

    Article  CAS  PubMed  Google Scholar 

  11. Zhu HH, Zhang XH, Qin YZ, Liu DH, Jiang H, Chen H, et al. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood. 2013;121(20):4056–62.

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Wu DP, Liu QF, Qin YZ, Wang JB, Xu LP, et al. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood. 2014;124(12):1880–6.

    Article  CAS  PubMed  Google Scholar 

  13. Pandolfi PP. In vivo analysis of the molecular genetics of acute promyelocytic leukemia. Oncogene. 2001;20:5726–35.

    Article  CAS  PubMed  Google Scholar 

  14. Shen ZX, Shi ZZ, Fang J, Gu W, Li JM, Zhu YM, et al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004;101(15):5328–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lo-Coco F, Ammatuna E. The biology of acute promyelocytic leukemia and its impact on diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2006:156–61, 514. https://www.ncbi.nlm.nih.gov/pubmed/17124055.

    Article  Google Scholar 

  16. Rahmé R, Thomas X, Recher C, Vey N, Delaunay J, Deconinck E, et al. Early death in acute promyelocytic leukemia (APL) in French centers: a multicenter study in 399 patients. Leukemia. 2014;28(12):2422–4.

    Article  PubMed  CAS  Google Scholar 

  17. Breccia M, Loglisci G, Loglisci MG, Ricci R, Diverio D, Latagliata R, et al. FLT3-ITD confers poor prognosis in patients with acute promyelocytic leukemia treated with AIDA protocols: long-term follow-up analysis. Haematologica. 2013;98(12):e161–3.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zelent A, Guidez F, Melnick A, Waxman S, Licht JD. Translocations of the RARalpha gene in acute promyelocytic leukemia. Oncogene. 2001;20:7186–203.

    Article  CAS  PubMed  Google Scholar 

  19. Melnick A, Licht JD. Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood. 1999;93:3167–215.

    CAS  PubMed  Google Scholar 

  20. Grimwade D, Jovanovic JV, Hills RK, Nugent EA, Patel Y, Flora R, et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol. 2009;27:3650–8.

    Article  CAS  PubMed  Google Scholar 

  21. Esteve J, Escoda L, Martin G, Rubio V, Díaz-Mediavilla J, González M, et al. Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy: benefit of an early intervention. Leukemia. 2007;21:446–52.

    Article  CAS  PubMed  Google Scholar 

  22. Meyer C, Burmeister T, Gröger D, Tsaur G, Fechina L, Renneville A, et al. The MLL recombinome of acute leukemias in 2017. Leukemia. 2018;32(2):273–84.

    Article  CAS  PubMed  Google Scholar 

  23. Chandra P, Luthra R, Zuo Z, Yao H, Ravandi F, Reddy N, et al. Acute myeloid leukemia with t(9;11)(p21-22;q23): common properties of dysregulated ras pathway signaling and genomic progression characterize de novo and therapy-related cases. Am J Clin Pathol. 2010;133(5):686–93.

    Article  PubMed  Google Scholar 

  24. Bindels EM, Havermans M, Lugthart S, Erpelinck C, Wocjtowicz E, Krivtsov AV, et al. EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs. Blood. 2012;119(24):5838–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mrózek K, Heinonen K, Lawrence D, Carroll AJ, Koduru PR, Rao KW, et al. Adult patients with de novo acute myeloid leukemia and t(9;11)(p22;q23) have a superior outcome to patients with other translocations involving band 11q23: a Cancer and Leukemia Group B study. Blood. 1997;90:4532–8.

    PubMed  Google Scholar 

  26. Gröschel S, Schlenk RF, Engelmann J, Rockova V, Teleanu V, Kühn MW, et al. Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol. 2013;31(1):95–103.

    Article  PubMed  Google Scholar 

  27. Scandura JM, Boccuni P, Cammenga J, Nimer SD. Transcription factor fusions in acute leukemia: variations on a theme. Oncogene. 2002;21(21):3422–44.

    Article  CAS  PubMed  Google Scholar 

  28. Slovak ML, Gundacker H, Bloomfield CD, Dewald G, Appelbaum FR, Larson RA, et al. A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ‘poor prognosis’ myeloid malignancies. Leukemia. 2006;20(7):1295–7.

    Article  CAS  PubMed  Google Scholar 

  29. Oyarzo MP, Lin P, Glassman A, Bueso-Ramos CE, Luthra R, Medeiros LJ. Acute myeloid leukemia with t(6;9)(p23;q34) is associated with dysplasia and a high frequency of flt3 gene mutations. Am J Clin Pathol. 2004;122(3):348–58.

    Article  CAS  PubMed  Google Scholar 

  30. Tarlock K, Alonzo TA, Moraleda PP, Gerbing RB, Raimondi SC, Hirsch BA, et al. Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is associated with poor outcome in childhood AML regardless of FLT3-ITD status: a report from the Children’s Oncology Group. Br J Haematol. 2014;166(2):254–9.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Gröschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BAM, Erpelinck C, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157(2):369–81.

    Article  PubMed  CAS  Google Scholar 

  32. Yamazaki H, Suzuki M, Otsuki A, Shimizu R, Bresnick EH, Engel JD, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell. 2014;25(4):415–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nucifora G, Laricchia-Robbio L, Senyuk V. EVI1 and hematopoietic disorders: history and perspectives. Gene. 2006;368:1–11.

    Article  CAS  PubMed  Google Scholar 

  34. Lugthart S, Gröschel S, Beverloo HB, Kayser S, Valk PJ, van Zelderen-Bhola SL, et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol. 2010;28(24):3890–8.

    Article  PubMed  Google Scholar 

  35. Gröschel S, Sanders MA, Hoogenboezem R, Zeilemaker A, Havermans M, Erpelinck C, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2015;125(1):133–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Haferlach C, Bacher U, Haferlach T, Dicker F, Alpermann T, Kern W, et al. The inv(3)(q21q26)/t(3;3)(q21;q26) is frequently accompanied by alterations of the RUNX1, KRAS and NRAS and NF1 genes and mediates adverse prognosis both in MDS and in AML: a study in 39 cases of MDS or AML. Leukemia. 2011;25(5):874–7.

    Article  CAS  PubMed  Google Scholar 

  37. Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet. 2001;28(3):220–1.

    Article  CAS  PubMed  Google Scholar 

  38. Inaba H, Zhou Y, Abla O, Adachi S, Auvrignon A, Beverloo HB, et al. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. Blood. 2015;126(13):1575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schweitzer J, Zimmermann M, Rasche M, von Neuhoff C, Creutzig U, Dworzak M, et al. Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial. Ann Hematol. 2015;94(8):1327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lindström MS. NPM1/B23: a multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int. 2011;2011:195209.

    Article  PubMed  CAS  Google Scholar 

  41. Colombo E, Marine JC, Danovi D, Falini B, Pelicci PG. Nucleophosmin regulates the stability and transcriptional activity of p53. Nat Cell Biol. 2002;4:529–33.

    Article  CAS  PubMed  Google Scholar 

  42. Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352(3):254–66.

    Article  CAS  PubMed  Google Scholar 

  43. Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A. 2014;111(7):2548–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Falini B, Mecucci C, Saglio G, Lo Coco F, Diverio D, Brown P, et al. NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia. Haematologica. 2008;93(3):439–42.

    Article  CAS  PubMed  Google Scholar 

  46. Haferlach C, Mecucci C, Schnittger S, Kohlmann A, Mancini M, Cuneo A, et al. AML with mutated NPM1 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 

  47. Cancer Genome Atlas Research Network, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.

    Article  CAS  Google Scholar 

  48. Döhner K, Schlenk RF, Habdank M, Scholl C, Rücker FG, Corbacioglu A, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106(12):3740–6.

    Article  PubMed  CAS  Google Scholar 

  49. Falini B, Macijewski K, Weiss T, Bacher U, Schnittger S, Kern W, et al. Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood. 2010;115(18):3776–86.

    Article  CAS  PubMed  Google Scholar 

  50. Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1909–18.

    Article  CAS  PubMed  Google Scholar 

  51. Pratcorona M, Brunet S, Nomdedéu J, Ribera JM, Tormo M, Duarte R, et al. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood. 2013;121(14):2734–8.

    Article  CAS  PubMed  Google Scholar 

  52. Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008;111(5):2776–84.

    Article  CAS  PubMed  Google Scholar 

  53. Schlenk RF, Kayser S, Bullinger L, Kobbe G, Casper J, Ringhoffer M, et al. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood. 2014;124(23):3441–9.

    Article  CAS  PubMed  Google Scholar 

  54. Loghavi S, Zuo Z, Ravandi F, Kantarjian HM, Bueso-Ramos C, Zhang L, et al. Clinical features of de novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations. J Hematol Oncol. 2014;7:74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113(13):3088–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Taskesen E, Bullinger L, Corbacioglu A, Sanders MA, Erpelinck CA, Wouters BJ, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011;117(8):2469–75.

    Article  CAS  PubMed  Google Scholar 

  57. Renneville A, Boissel N, Gachard N, Naguib D, Bastard C, de Botton S, et al. The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication. Blood. 2009;113(21):5090–3.

    Article  CAS  PubMed  Google Scholar 

  58. Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol. 2010;28(16):2739–47.

    Article  CAS  PubMed  Google Scholar 

  59. Fasan A, Haferlach C, Alpermann T, Jeromin S, Grossmann V, Eder C, et al. The role of different genetic subtypes of CEBPA mutated AML. Leukemia. 2014;28(4):794–803.

    Article  CAS  PubMed  Google Scholar 

  60. Bacher U, Schnittger S, Macijewski K, Grossmann V, Kohlmann A, Alpermann T, et al. Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood. 2012;119(20):4719–22.

    Article  CAS  PubMed  Google Scholar 

  61. Paietta E, Racevskis J, Bennett JM, Neuberg D, Cassileth PA, Rowe JM, et al. Biologic heterogeneity in Philadelphia chromosome-positive acute leukemia with myeloid morphology: the Eastern Cooperative Oncology Group experience. Leukemia. 1998;12(12):1881–5.

    Article  CAS  PubMed  Google Scholar 

  62. Soupir CP, Vergilio JA, Dal Cin P, 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.

    Article  PubMed  Google Scholar 

  63. Konoplev S, Yin CC, Kornblau SM, Kantarjian HM, Konopleva M, Andreeff M, et al. Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia. Leuk Lymphoma. 2013;54(1):138–44.

    Article  CAS  PubMed  Google Scholar 

  64. Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241–7.

    Article  CAS  PubMed  Google Scholar 

  65. Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Weinberg OK, Seetharam M, Ren L, Seo K, Ma L, Merker JD, et al. Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood. 2009;113(9):1906–8.

    Article  CAS  PubMed  Google Scholar 

  67. Arber DA, Stein AS, Carter NH, Ikle D, Forman SJ, Slovak ML. Prognostic impact of acute myeloid leukemia classification. Importance of detection of recurring cytogenetic abnormalities and multilineage dysplasia on survival. Am J Clin Pathol. 2003;119(5):672–80.

    Article  PubMed  Google Scholar 

  68. Hasserjian RP, Campigotto F, Klepeis V, Fu B, Wang SA, Bueso-Ramos C, et al. De novo acute myeloid leukemia with 20–29% blasts is less aggressive than acute myeloid leukemia with ≥30% blasts in older adults: a Bone Marrow Pathology Group study. Am J Hematol. 2014;89(11):E193–9.

    Article  CAS  PubMed  Google Scholar 

  69. Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125(9):1367–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Devillier R, Mansat-De Mas V, Gelsi-Boyer V, Demur C, Murati A, Corre J, et al. Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes. Oncotarget. 2015;6(10):8388–96.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ohgami RS, Ma L, Merker JD, Gotlib JR, Schrijver I, Zehnder JL, et al. Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations. Mod Pathol. 2015;28(5):706–14.

    Article  CAS  PubMed  Google Scholar 

  73. Morton LM, Dores GM, Tucker MA, Kim CJ, Onel K, Gilbert ES, et al. Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975–2008. Blood. 2013;121(15):2996–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Radivoyevitch T, Sachs RK, Gale RP, Molenaar RJ, Brenner DJ, Hill BT, et al. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation. Leukemia. 2016;30(2):285–94.

    Article  CAS  PubMed  Google Scholar 

  75. Mauritzson N, Albin M, Rylander L, Billström R, Ahlgren T, Mikoczy Z, et al. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001. Leukemia. 2002;16(12):2366–78.

    Article  CAS  PubMed  Google Scholar 

  76. Rowley JD, Olney HJ. International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: overview report. Genes Chromosomes Cancer. 2002;33(4):331–45.

    Article  PubMed  Google Scholar 

  77. Kayser S, Döhner K, Krauter J, Köhne CH, Horst HA, Held G, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117(7):2137–45.

    Article  CAS  PubMed  Google Scholar 

  78. Nardi V, Winkfield KM, Ok CY, Niemierko A, Kluk MJ, Attar EC, et al. Acute myeloid leukemia and myelodysplastic syndromes after radiation therapy are similar to de novo disease and differ from other therapy-related myeloid neoplasms. J Clin Oncol. 2012;30(19):2340–7.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Andersen MK, Larson RA, Mauritzson N, Schnittger S, Jhanwar SC, Pedersen-Bjergaard J. Balanced chromosome abnormalities inv(16) and t(15;17) in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop. Genes Chromosomes Cancer. 2002;33(4):395–400.

    Article  PubMed  Google Scholar 

  80. Borthakur G, Lin E, Jain N, Estey EE, Cortes JE, O’Brien S, et al. Survival is poorer in patients with secondary core-binding factor acute myelogenous leukemia compared with de novo core-binding factor leukemia. Cancer. 2009;115(14):3217–21.

    Article  PubMed  Google Scholar 

  81. Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Fu B, Tang G, et al. Mutational profiling of therapy-related myelodysplastic syndromes and acute myeloid leukemia by next generation sequencing, a comparison with de novo diseases. Leuk Res. 2015;39(3):348–54.

    Article  CAS  PubMed  Google Scholar 

  82. Shih AH, Chung SS, Dolezal EK, Zhang SJ, Abdel-Wahab OI, Park CY, et al. Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Haematologica. 2013;98(6):908–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Roy A, Cowan G, Mead AJ, Filippi S, Bohn G, Chaidos A, et al. Perturbation of fetal liver hematopoietic stem and progenitor cell development by trisomy 21. Proc Natl Acad Sci U S A. 2012;109(43):17579–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Tunstall-Pedoe O, Roy A, Karadimitris A, de la Fuente J, Fisk NM, Bennett P, et al. Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations. Blood. 2008;112(12):4507–11.

    Article  CAS  PubMed  Google Scholar 

  85. Chou ST, Opalinska JB, Yao Y, Fernandes MA, Kalota A, Brooks JS, et al. Trisomy 21 enhances human fetal erythro-megakaryocytic development. Blood. 2008;112(12):4503–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, et al. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet. 2002;32(1):148–52.

    Article  CAS  PubMed  Google Scholar 

  87. Alford KA, Reinhardt K, Garnett C, Norton A, Böhmer K, von Neuhoff C, et al. Analysis of GATA1 mutations in Down syndrome transient myeloproliferative disorder and myeloid leukemia. Blood. 2011;118(8):2222–38.

    Article  CAS  PubMed  Google Scholar 

  88. Roberts I, Alford K, Hall G, Juban G, Richmond H, Norton A, et al. GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia. Blood. 2013;122(24):3908–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45(11):1293–9.

    Article  CAS  PubMed  Google Scholar 

  90. Nikolaev SI, Santoni F, Vannier A, Falconnet E, Giarin E, Basso G, et al. Exome sequencing identifies putative drivers of progression of transient myeloproliferative disorder to AMKL in infants with Down syndrome. Blood. 2013;122(4):554–61.

    Article  CAS  PubMed  Google Scholar 

  91. Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17(2):277–82.

    Article  CAS  PubMed  Google Scholar 

  92. Bolouri H, Farrar JE, Triche T Jr, Ries RE, Lim EL, Alonzo TA, et al. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat Med. 2018;24(1):103–12.

    Article  CAS  PubMed  Google Scholar 

  93. Harrison CJ, Hills RK, Moorman AV, Grimwade DJ, Hann I, Webb DK, et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol. 2010;28(16):2674–81.

    Article  PubMed  Google Scholar 

  94. von Neuhoff C, Reinhardt D, Sander A, Zimmermann M, Bradtke J, Betts DR, et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol. 2010;28(16):2682–9.

    Article  CAS  Google Scholar 

  95. Sandahl JD, Kjeldsen E, Abrahamsson J, Ha SY, Heldrup J, Jahnukainen K, et al. Ploidy and clinical characteristics of childhood acute myeloid leukemia: a NOPHO-AML study. Genes Chromosomes Cancer. 2014;53(8):667–75.

    Article  CAS  PubMed  Google Scholar 

  96. Rasche M, von Neuhoff C, Dworzak M, Bourquin JP, Bradtke J, Göhring G, et al. Genotype-outcome correlations in pediatric AML: the impact of a monosomal karyotype in trial AML-BFM 2004. Leukemia. 2017;31(12):2807–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009;114(12):2489–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Huret JL, Brizard A, Slater R, Charrin C, Bertheas MF, Guilgot F, et al. Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients—updated published cases and 16 new observations. Leukemia. 1993;7(2):152–60.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Eric Y. Loo

  2. Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

    Eric Y. Loo

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  1. Dartmouth–Hitchcock Medical Center, Lebanon, NH, USA

    Laura J. Tafe

  2. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Maria E. Arcila

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Loo, E.Y. (2020). Acute Myeloid Neoplasms. In: Tafe, L., Arcila, M. (eds) Genomic Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-22922-1_14

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