Acute Myeloid Leukemia (AML) Classification

Evolution of AML Classification

  • Beginning in the 1970s, AML was classified according to the FAB (French-American-British) system, which was based on routine cytochemical stains and morphology to differentiate AML from ALL1
  • AML subtypes were based on the type of cell where the leukemia initiated, and the level of myeloid and monocytic differentiation1
  • FAB classification did not account for many underlying factors that may affect prognosis and therapy response, nor the molecular heterogeneity of the disease1
  • In 1999, the WHO developed a new AML classification system that stratified patients using cytogenetics in order to refine prognosis and treatment strategies for different subgroups2
  • WHO classification lowered the threshold for diagnosing AML from 30% to 20% blasts in bone marrow or peripheral blood2
  • In 2003, the International Working Group for Diagnosis Standardization of Response Criteria accepted WHO criteria as the standard for diagnosing AML3
  • WHO has amended diagnostic criteria to include additional genetic and cytogenetic abnormalities as well as new provisional categories for certain molecular markers, including BCR-ABL1 rearrangement and RUNX1 mutation4

WHO 2016 AML Classification

The WHO 2016 classification defines acute leukemia as ≥20% blasts in the marrow or blood. A diagnosis of AML may be made with less than 20% blasts in patients with the following cytogenetic abnormalities: t(15;17), t(8;21), t(16;16), inv(16).5

A diagnosis is based on multidisciplinary diagnostic studies which include morphology, immunophenotyping, history/physical, laboratory evaluations, bone marrow analysis with cytogenetics, and a comprehensive evaluation of several molecular markers.1

WHO classification divides AML into several subgroups based on molecular and cytogenetic abnormalities1,4:

Group Subgroups
AML with recurrent genetic abnormalities AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22), CBFβ/MYH11
APL with PML/RARA
AML with t(9;11)(p21.3;q23.3); MLLT3-KMT2A
AML with t(6;9)(p23;q34.1); DEK-NUP214
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
AML (megakaryoblastic) with t(1;22)(p13.3;q13.3); RBM15-MKL1
Provisional entity: AML with BCR-ABL1
AML with mutated NPM1
AML with biallelic mutations of CEBPA
Provisional entity: AML with mutated RUNX1
AML with myelodysplasia-related changes
Therapy-related myeloid neoplasms
AML, not otherwise specified AML with minimal differentiation
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic/monocytic leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis
Pure erythroid leukemia
In the 2016 classification, myeloblasts are always counted as a percentage of total marrow cells.
Bold text in the table represents updates in the WHO 2016 Classification Scheme.5

References: 1. Acute Myeloid Leukemia (AML) Subtypes and Prognostic Indicators. American Cancer Society website. https://www.cancer.org/cancer/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html. Accessed March 3, 2021. 2. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17(12):3835-3849. 3. Cheson BD, Bennett JM, Kopecky KJ, et al, International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642-4649. 4. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-951. 5. 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):2391-2405.