Acute myeloid leukemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2], Carlos A Lopez, M.D. [3], Shyam Patel [4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Overview

There are three classification systems for acute myeloid leukemia. These classifications include French-American-British (FAB) , the World Health Organization (WHO), and the European LeukemiaNet (ELN) . The original classification was the French-American-British (FAB) classification, and the most recent classification was the 2017 European LeukemiaNet (ELN) classification. There are several broad classification schemes for acute promyelocytic leukemia. The most well-accepted classification scheme is risk-based classification, which categories patients into low-risk, intermediate-risk, or high-risk based on the white blood cell count and platelet count. Another classification scheme is based on the origin of the leukemia, which categorized patients as having de novo or therapy-related disease. A final classification scheme is cytogenetic-based, in which case specific chromosomal abnormalities are used to stratify patients.

Classification of Acute myeloid leukemia:

French-American-British classification

The French-American-British (FAB) classification system divided acute myeloid leukemia into 8 sub-types, M0 through to M7, based on the type of cell from which the leukemia developed and its degree of maturity. This was done by examining the appearance of the malignant cells under light microscopy and/or by using cytogenetics to characterize any underlying chromosomal abnormalities. The sub-types have varying prognoses and responses to therapy. Although the World Health Organization (WHO) classification (see below) may be more useful, the FAB system is still widely used as of mid-2006.

The eight FAB sub-types are:[1]

Type Name Cytogenetics
M0 Minimally differentiated AML
M1 Acute myeloblastic leukemia, without maturation
M2 Acute myeloblastic leukemia, with granulocytic maturation t(8;21)(q22;q22), t(6;9)
M3 Promyelocytic, or Acute promyelocytic leukemia (APL) t(15;17)
M4 Acute myelomonocytic leukemia inv(16)(p13q22), del(16q)
M4eo Myelomonocytic together with bone marrow eosinophilia inv(16), t(16;16)
M5 Acute monoblastic leukemia (M5a) or Acute monocytic leukemia (M5b) del (11q), t(9;11), t(11;19)
M6 Acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b)
M7 Acute megakaryoblastic leukemia t(1;22)

World Health Organization classification

The World Health Organization (WHO) classification of acute myeloid leukemia attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria. Each of the WHO categories contains numerous descriptive sub-categories of interest to hematopathologists and oncologists; however, most of the clinically significant information in the WHO schema is communicated via categorization into one of the five sub-types listed below. The 2016 revision of the WHO classification was recently developed.

The sub-types of acute myeloid leukemia are shown below:[2]

Name Description ICD-O
Acute myeloid leukemia with characteristic genetic abnormalities This category includes:

Patients with acute myeloid leukemia in this category generally have a high rate of remission and a better prognosis compared to other types of acute myeloid leukemia.

Multiple
Acute myeloid leukemia with multilineage dysplasia This category includes patients who have had a prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) that transforms into acute myeloid leukemia. This category of acute myeloid leukemia occurs most often in elderly patients and often has a worse prognosis. M9895/3
Acute myeloid leukemia and MDS, therapy-related This category includes patients who have had prior chemotherapy and/or radiation and subsequently develop acute myeloid leukemia or MDS. These leukemias may be characterized by specific chromosomal abnormalities, and often carry a worse prognosis. M9920/3
Acute myeloid leukemia not otherwise categorized This category includes sub-types of acute myeloid leukemia that do not fall into the above categories. M9861/3

European LeukemiaNet classification

The European LeukemiaNet classification is a risk-based classification system that was recently revised in 2017.[6]

Name Description
Favorable risk Includes:
  • AML with translocations between chromosome 8 and chromosome 21; t(8;21); RUNX1/RUNX1T1
  • AML with inversions in chromosome 16; inv(16); CBFB/MYH11
  • AML with mutant NPM1 and wild-type FLT3
  • AML with biallelic CEBPalpha mutation
Intermediate risk Includes:
  • AML with mutant NPM1 and mutant FLT3 (FLT3-ITD)
  • AML with wild-type NPM1 and wild-type FLT3 (no FLT3-ITD)
  • AML with translocations between chromosome 9 and chromosome 21 (MLLT3-KMT2A)
  • AML with cytogenetic abnormalities not classified as favorable or adverse
Adverse risk Includes:
  • AML with translocations between chromosome 6 and chromosome 9
  • AML with inversion of chromosome 3
  • AML with translocations involving chromosome 11q23
  • AML with translocations between chromosome 6 and chromosome 9
  • AML with monosomy 5 or 7
  • AML with complex karyotype (2 or more cytogenetic abnormalities)
  • AML with mutant RUNX1, mutant ASXL1, or mutant TP53

Classification of acute promyelocytic leukemia:

Acute promyelocytic leukemia is further classified in to the following several classification schemes.

Based on Risk

Based on etiology

  • De novo disease:
    • De novo acute promyelocytic leukemia is the most common sub-type.
    • This refers to development of the disease in the absence of prior cytotoxic therapy or prior precursor conditions.
    • De novo acute promyelocytic leukemia is due to a sporadic events in cells, without prior DNA damaging insults. This is in contrast to therapy-related disease.
Chemotherapeutic agents
Topoisomerase II inhibitors:
Alkylating agents:
Other chemotherapeutic agents:

Based on cytogenetics

Cytogenetics
Complex karyotype
  • Complex karyotype is defined as the presence of two or more chromosomal abnormities.
  • Complex karyotype acute promyelocytic leukemia is associated with worse prognosis and lower rates of complete remission, similar to complex karyotype acute myeloid leukemia[11].
  • Patients with complex karyotype are more likely to have a TP53 mutation and are more likely to be resistant to chemotherapy.[11]
Trisomy 8
Tetraploidy
t(8;21)

References

  1. Bennett J, Catovsky D, Daniel M, Flandrin G, Galton D, Gralnick H, Sultan C (1976). "Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group". Br J Haematol. 33 (4): 451–8. PMID 188440.
  2. Vardiman J, Harris N, Brunning R (2002). "The World Health Organization (WHO) classification of the myeloid neoplasms". Blood. 100 (7): 2292–302. PMID 12239137. Full text.
  3. Reikvam H, Hatfield KJ, Kittang AO, Hovland R, Bruserud Ø (2011). "Acute myeloid leukemia with the t(8;21) translocation: clinical consequences and biological implications". J Biomed Biotechnol. 2011: 104631. doi:10.1155/2011/104631. PMC 3100545. PMID 21629739.
  4. Pulikkan JA, Castilla LH (2018). "Preleukemia and Leukemia-Initiating Cell Activity in inv(16) Acute Myeloid Leukemia". Front Oncol. 8: 129. doi:10.3389/fonc.2018.00129. PMC 5932169. PMID 29755956.
  5. Grimwade D, Ivey A, Huntly BJ (2016). "Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance". Blood. 127 (1): 29–41. doi:10.1182/blood-2015-07-604496. PMC 4705608. PMID 26660431.
  6. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T; et al. (2017). "Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel". Blood. 129 (4): 424–447. doi:10.1182/blood-2016-08-733196. PMC 5291965. PMID 27895058.
  7. 7.0 7.1 Coombs CC, Tavakkoli M, Tallman MS (2015). "Acute promyelocytic leukemia: where did we start, where are we now, and the future". Blood Cancer J. 5: e304. doi:10.1038/bcj.2015.25. PMC 4450325. PMID 25885425.
  8. McCulloch D, Brown C, Iland H (2017). "Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives". Onco Targets Ther. 10: 1585–1601. doi:10.2147/OTT.S100513. PMC 5359123. PMID 28352191.
  9. 9.0 9.1 Zhang YC, Zhou YQ, Yan B, Shi J, Xiu LJ, Sun YW; et al. (2015). "Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: a case report". World J Gastroenterol. 21 (14): 4402–7. doi:10.3748/wjg.v21.i14.4402. PMC 4394105. PMID 25892894.
  10. 10.0 10.1 Zahid MF, Parnes A, Savani BN, Litzow MR, Hashmi SK (2016). "Therapy-related myeloid neoplasms - what have we learned so far?". World J Stem Cells. 8 (8): 231–42. doi:10.4252/wjsc.v8.i8.231. PMC 4999650. PMID 27621757.
  11. 11.0 11.1 11.2 11.3 11.4 Chen C, Huang X, Wang K, Chen K, Gao D, Qian S (2018). "Early mortality in acute promyelocytic leukemia: Potential predictors". Oncol Lett. 15 (4): 4061–4069. doi:10.3892/ol.2018.7854. PMC 5835847. PMID 29541170.
  12. Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M (July 1993). "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript". EMBO J. 12 (7): 2715–21. PMC 413521. PMID 8334990.

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