Blood Res.  2020 Jul;55(S1):S1-S4. 10.5045/br.2020.S001.

Classification of acute myeloid leukemia

• Hwang SM

• KMID: 2504735
• DOI: http://doi.org/10.5045/br.2020.S001

Abstract

The World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues was revised in 2017 on the basis of recent high-throughput sequencing and gene expression data on hematologic malignancies. This review explores the current WHO classification of acute myeloid leukemia (AML) and related precursor neoplasms, highlighting the changes made in the current edition and focusing on the diagnosis of AML.

Keyword

Acute myeloid leukemia; Classification; Diagnosis

Reference

1. Arber DA, Brunning RD, Le Beau MM, et al. Swerdlow SH, Campo E, Harris NL, editors. 2008. Acute myeloid leukaemia (AML) and related precursor neoplasms. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. IARC Press;Lyon, France: p. 110–44.

2. Jaffe ES, Harris NL, Stein H, Vardiman JW. 2001. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. 3rd ed. IARC Press;Lyon, France: p. 75–105.

3. Arber DA, Brunning RD, Le Beau MM, et al. Swerdlow SH, Campo E, Harris NL, editors. 2017. Acute myeloid leukaemia and related precursor neoplasms. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. IARC Press;Lyon, France: p. 130–71.

4. Neuendorff NR, Burmeister T, Dörken B, Westermann J. 2016; BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features. Ann Hematol. 95:1211–21. DOI: 10.1007/s00277-016-2721-z. PMID: 27297971.

5. Soupir CP, Vergilio JA, Dal Cin P, et al. 2007; 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. 127:642–50. DOI: 10.1309/B4NVER1AJJ84CTUU. PMID: 17369142.

6. Konoplev S, Yin CC, Kornblau SM, et al. 2013; Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia. Leuk Lymphoma. 54:138–44. DOI: 10.3109/10428194.2012.701739. PMID: 22691121. PMCID: PMC3925981.

7. Papaemmanuil E, Gerstung M, Bullinger L, et al. 2016; Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 374:2209–21. DOI: 10.1056/NEJMoa1516192. PMID: 27276561. PMCID: PMC4979995.

8. Tallman MS, Wang ES, Altman JK, et al. 2019; Acute myeloid leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 17:721–49. DOI: 10.6004/jnccn.2019.0028. PMID: 31200351.

9. Döhner H, Estey E, Grimwade D, et al. 2017; Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 129:424–47. DOI: 10.1182/blood-2016-08-733196. PMID: 27895058. PMCID: PMC5291965.

10. Dufour A, Schneider F, Metzeler KH, et al. 2010; Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol. 28:570–7. DOI: 10.1200/JCO.2008.21.6010. PMID: 20038735.

11. Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. 2009; 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. 113:3088–91. DOI: 10.1182/blood-2008-09-179895. PMID: 19171880. PMCID: PMC2662648.

12. Gaidzik VI, Teleanu V, Papaemmanuil E, et al. 2016; RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia. 30:2160–8. DOI: 10.1038/leu.2016.126. PMID: 27137476.

13. Stengel A, Kern W, Meggendorfer M, et al. 2018; Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML. Leukemia. 32:295–302. DOI: 10.1038/leu.2017.239. PMID: 28751771.

14. Schnittger S, Dicker F, Kern W, et al. 2011; RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood. 117:2348–57. DOI: 10.1182/blood-2009-11-255976. PMID: 21148331.

15. Daver N, Schlenk RF, Russell NH, Levis MJ. 2019; Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 33:299–312. DOI: 10.1038/s41375-018-0357-9. PMID: 30651634. PMCID: PMC6365380.

16. Kottaridis PD, Gale RE, Frew ME, et al. 2001; The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 98:1752–9. DOI: 10.1182/blood.V98.6.1752. PMID: 11535508.

17. Arber DA, Stein AS, Carter NH, Ikle D, Forman SJ, Slovak ML. 2003; Prognostic impact of acute myeloid leukemia classification: importance of detection of recurring cytogenetic abnormalities and multilineage dysplasia on survival. Am J Clin Pathol. 119:672–80. DOI: 10.1309/EM7KCQR4GLMHRCX4. PMID: 12760285.

18. Gahn B, Haase D, Unterhalt M, et al. 1996; De novo AML with dysplastic hematopoiesis: cytogenetic and prognostic significance. Leukemia. 10:946–51. PMID: 8667650.

19. Bacher U, Schnittger S, Macijewski K, et al. 2012; Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood. 119:4719–22. DOI: 10.1182/blood-2011-12-395574. PMID: 22442349.

20. Falini B, Macijewski K, Weiss T, et al. 2010; Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood. 115:3776–86. DOI: 10.1182/blood-2009-08-240457. PMID: 20203266.

21. Haferlach C, Mecucci C, Schnittger S, et al. 2009; AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood. 114:3024–32. DOI: 10.1182/blood-2009-01-197871. PMID: 19429869.

22. Schlenk RF, Taskesen E, van Norden Y, et al. 2013; The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. 122:1576–82. DOI: 10.1182/blood-2013-05-503847. PMID: 23863898.

23. McNerney ME, Godley LA, Le Beau MM. 2017; Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 17:513–27. DOI: 10.1038/nrc.2017.60. PMID: 28835720. PMCID: PMC5946699.

24. Takahashi K, Wang F, Kantarjian H, et al. 2017; Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study. Lancet Oncol. 18:100–11. DOI: 10.1016/S1470-2045(16)30626-X. PMID: 27923552. PMCID: PMC5405697.

25. Gillis NK, Ball M, Zhang Q, et al. 2017; Clonal haemopoiesis and therapy-related myeloid malignancies in elderly patients: a proof-of-concept, case-control study. Lancet Oncol. 18:112–21. DOI: 10.1016/S1470-2045(16)30627-1. PMID: 27927582.

26. Godley LA, Larson RA. 2008; Therapy-related myeloid leukemia. Semin Oncol. 35:418–29. DOI: 10.1053/j.seminoncol.2008.04.012. PMID: 18692692. PMCID: PMC2600445.

27. Larson RA. 2009; Therapy-related myeloid neoplasms. Haematologica. 94:454–9. DOI: 10.3324/haematol.2008.005157. PMID: 19336749. PMCID: PMC2663607.

28. Zuo Z, Medeiros LJ, Chen Z, et al. 2012; Acute myeloid leukemia (AML) with erythroid predominance exhibits clinical and molecular characteristics that differ from other types of AML. PLoS One. 7:e41485. DOI: 10.1371/journal.pone.0041485. PMID: 22844482. PMCID: PMC3402404.

29. Ryu S, Park HS, Kim SM, et al. 2018; Shifting of erythroleukemia to myelodysplastic syndrome according to the revised WHO classification: biologic and cytogenetic features of shifted erythroleukemia. Leuk Res. 70:13–9. DOI: 10.1016/j.leukres.2018.04.015. PMID: 29729583.

30. Hasserjian RP, Zuo Z, Garcia C, et al. 2010; Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood. 115:1985–92. DOI: 10.1182/blood-2009-09-243964. PMID: 20040759. PMCID: PMC2942006.

31. Pileri SA, Ascani S, Cox MC, et al. 2007; Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 21:340–50. DOI: 10.1038/sj.leu.2404491. PMID: 17170724.

32. Campidelli C, Agostinelli C, Stitson R, Pileri SA. 2009; Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol. 132:426–37. DOI: 10.1309/AJCP1ZA7HYZKAZHS. PMID: 19687319.

33. Li Z, Stölzel F, Onel K, et al. 2015; Next-generation sequencing reveals clinically actionable molecular markers in myeloid sarcoma. Leukemia. 29:2113–6. DOI: 10.1038/leu.2015.81. PMID: 25787914. PMCID: PMC4575593.

34. Fong CT, Brodeur GM. 1987; Down's syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis. Cancer Genet Cytogenet. 28:55–76. DOI: 10.1016/0165-4608(87)90354-2. PMID: 2955886.

35. Webb D, Roberts I, Vyas P. 2007; Haematology of Down syndrome. Arch Dis Child Fetal Neonatal Ed. 92:F503–7. DOI: 10.1136/adc.2006.104638. PMID: 17804520. PMCID: PMC2675407.

36. Roy A, Roberts I, Vyas P. 2012; Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome. Semin Fetal Neonatal Med. 17:196–201. DOI: 10.1016/j.siny.2012.02.010. PMID: 22421527.

37. Lange BJ, Kobrinsky N, Barnard DR, et al. 1998; Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891. Blood. 91:608–15. PMID: 9427716.

38. Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. 2003; GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood. 101:4301–4. DOI: 10.1182/blood-2003-01-0013. PMID: 12586620.

39. Taub JW, Berman JN, Hitzler JK, et al. 2017; Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children's Oncology Group AAML0431 trial. Blood. 129:3304–13. DOI: 10.1182/blood-2017-01-764324. PMID: 28389462. PMCID: PMC5482102.