AML classification (WHO)

Classification of acute myeloid leukemia (World Health Organisation, 2008)

ClassificationCriteria
AML with recurrent genetic abnormalitiesBone marrow or peripheral blood blasts ≥ 20%, or myeloid sarcoma, AND one of the following cytogenetic abnormalities:
  • t(8;21)(q22;q22); RUNX1-RUNX1T1*
  • inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11*
  • t(15;17)(q22;q12); PML-RARA*
  • t(9;11)(p22;q23); MLLT3-MLL
  • t(6;9)(p23;q34) DEK-NUP214
  • inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1
  • t(1;22)(p13;q13); RBM15-MKL1
  • AML with mutated NPM1 (provisional entity)
  • AML with mutated CEBPA (provisional entity)
* cases with these genetic abnormalities are considered as AML regardless of blast count
Therapy-related myeloid neoplasmsAML with history of treatment of an unrelated disorder with any of the following agents:
  • Akylating agents (melphalan, cyclophosphamide, nitrogen mustard, chlorambucil, busulfan, carboplatin, cisplatin, dacarbazine, procarbazine, carmustine, mitomycin C, thiotepa, lomustine)
  • Ionizing radiation (large fields including active bone marrow)
  • Topoisomerase II inhibitors (etoposide, teniposide, doxorubicin, daunorubicin, mitoxantrone, amsacrine, actinomycin)
  • Others (thiopurines, mycophenolate, fludarabine, vincristine, vinblastine, vindesine, paclitaxel, docetaxel)
AML with myelodysplasia-related changes≥ 20% blood or marrow blasts and ANY of the following:
  • previous history of myelodysplastic syndrome
  • myelodysplastic syndrome-related cytogenetic abnormality (1)
  • multilineage dysplasia
and ABSENCE of BOTH:
  • prior cytotoxic therapy for an unrelated disease
  • recurring cytogenetic abnormality as described in AML with recurrent cytogenetic abnormalities
AML, not otherwise specifiedAML not meeting any of the above criteria. Categories are:
  • AML with minimal differentiation (no morphologic evidence of myeloid differentiation, immunophenotyping negative for antigens associated with myeloid or monocytic maturation e.g. CD11b, CD15, CD14, CD64, CD65)
  • AML without maturation (blasts constitute ≥90% of non-erythroid cells)
  • AML with maturation (≥ 20% blasts and evidence of maturation with ≥10% maturing cells of neutrophil lineage; cells of monocyte lineage are < 20%)
  • Acute myelomonocytic leukemia (marrow or blood blasts ≥ 20% including promonocytes; neutrophils and their precursors and monocytes and their precursors each comprise ≥ 20% of marrow cells)
  • Acute monoblastic and monocytic leukemia (≥80% of the leukaemic cells are monoblasts, promonocytes or monocytes; neutrophil component is < 20%; if > 50% of monocytic cells are monoblasts, label as acute monoblastic leukemia; if > 50% of monocytic cells are promonocytes, label as acute monocytic leukemia)
  • Acute erythroid leukemia (acute erythroid/myeloid leukemia if ≥ 50% of marrow cells are erythroid precursors AND ≥ 20% of nucleated non-erythroid cells are myeloblasts; pure erythroid leukemia if ≥ 80% of marrow cells are immature erythroblasts with minimal maturation)
  • Acute megakaryoblastic leukemia (≥ 50% of blasts are of megakaryocyte lineage, expressing CD41 and/or CD61; myeloid proliferations related to Down syndrome are classified separately)
  • Acute basophilic leukemia
  • Acute panmyelosis with myelofibrosis
Myeloid sarcomaTumor mass of myeloid blasts with or without maturation at an anatomical site other than the bone marrow (if meets any of the criteria above, categorise as the relevant AML with a myeloid sarcoma)
(1) Cytogenetic abnormalities sufficient to diagnose AML with myelodysplasia-related features when ≥20% blood or marrow blasts are present:

  • Complex karyotype (≥3 unrelated abnormalities, none of which are recorded in the AML with recurrent genetic abnormalities subgroup)
  • Unbalanced abnormalities: -7/del(7q), -5/del(5q), i(17q)/t(17p), -13/del(13q), del(11q), del(12p)/t(12p), del(9q), idic(X)(q13)
  • Balanced abnormalities: t(11;16)(q23;p13.3)*, t(3;21)(q26.2;q22.1)*, t(1;3)(p36.3;q21.1), t(2;11)(p21;q23)*, t(5;12)(q33;p12), t(5;7)(q33;q11.2), t(5;17)(q33;p13), t(5;10)(q33;q21), t(3;5)(q25;q34)

* these abnormalities most commonly occur in therapy-related disease, which must be excluded before using as evidence for AML with myelodysplasia-related features

This classification of acute myeloid leukemia (acute myelogenous leukemia) was published in the 4th edition of the World Health Organisation book, “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues” in 2008.1

The diagnosis of acute myeloid leukemia is made when blasts account for ≥20% of nucleated cells in the bone marrow or peripheral blood. Acute myeloid leukemia may also be diagnosed with a lower percentage of blasts in the presence of certain genetic abnormalities (t(8;21), inv(16), t(16;16) or t(15;17)), or with myeloid sarcoma.

When applying the WHO classification, the categories highest in the table to the left take precedence over those lower in the table. For instance, AML following cytotoxic chemotherapy and with t(8;21) will be classified as “AML with t(8;21)”, and not as a “therapy-related myeloid neoplasm”. Similarly, AML arising after myelodysplastic syndrome but meeting the morphologic criteria for acute myelomonocytic leukemia will be classified as “AML with myelodysplasia-related changes”, and not as “acute myelomonocytic leukemia”.