Acute myeloid
leukemia (AML)

  • Method:
  • Anticoagulant:
  • Recommendation:
  • Method:
  • Anticoagulant:
  • Recommendation:
  • Method:
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
  • Method:
    Chromosome analysis
  • Anticoagulant:
  • Recommendation:
  • Method:
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
  • Method:
    Molecular genetics
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:

Based on the current guidelines and the current state of research, there are different diagnostic recommendations for patients with acute myeloid leukemia. We have summarized the most important information on classification and diagnostic methods at MLL. In addition, we provide further links on prognosis and therapy in acute myeloid leukemia, so that you can inform yourself in more detail.

AML: Classification

Acute myeloid leukemias (AML) may arise de novo, after prior cytotoxic and/or radiotherapy (AML-pCT), or secondarily from preexisting myelodysplastic/myeloproliferative disease or MDS. In the current classification, the WHO distinguishes between AML with defining genetic abnormalities and AML, defined by differentiation (Table 1) as well as myeloid sarcoma (WHO 2022).

Tab. 1: AML with defining genetic abnormalities and AML, defined by differentiation (WHO 2022)

AML with defining genetic abnormalities

AML, defined by differentiation

Acute promyelocytic leukemia with PML::RARA fusion

AML with minimal differentiation

AML with RUNX1::RUNX1T1 fusion

AML without maturation

AML with CBFB::MYH11 fusion

AML with maturation

AML with DEK::NUP214 fusion

Acute basophilic leukemia

AML with RBM15::MRTFA fusion

Acute myelomonocytic leukemia

AML with BCR::ABL1 fusion

Acute monocytic leukemia

AML with KMT2A rearrangement

Acute erythroid leukemia

AML with MECOM rearrangement

Acute megakaryoblastic leukemia

AML with NUP98 rearrangement


AML with NPM1 mutation


AML with CEBPA mutation


AML, myelodysplasia-related (AML-MR)


AML with other defined genetic alterations


In contrast to the previous 2017 version of the WHO classification, the previous criterion of at least 20% blasts in peripheral blood or bone marrow (Swerdlow et al. 2017) is omitted for AML with defining genetic abnormalities – with the exception of AML with BCR::ABL1 fusion, AML with CEBPA mutation and AML-MR. For AML with BCR::ABL1 fusion, this serves to differentiate it from CML. For the diagnosis of AML with CEBPA mutation, the blast criterion must also still be met due to insufficient data to date (WHO 2022).

Important changes in the new WHO classification also concern the AML-MR subtype (previously AML with myelodysplasia-related changes). Essential diagnostic criteria include a blast count of at least 20% in peripheral blood or bone marrow. However, for this subtype, morphology is no longer the sole diagnostic criterion, cytogenetic criteria have been updated, and a mutation-based definition has been introduced using 8 genes:

Defining cytogenetic abnormalities in AML-MR:

  • Complex karyotype (≥ 3 abnormalities)
  • 5q deletion or loss of 5q due to unbalanced translocation
  • Monosomy 7, 7q deletion, or loss of 7q due to unbalanced translocation
  • 11q deletion
  • 12p deletion or loss of 12p due to unbalanced translocation
  • Monosomy 13 or 13q deletion
  • 17p deletion or loss of 17p due to unbalanced translocation
  • Isochromosome 17q
  • idic(X)(q13)

Defining somatic mutations in AML-MR:

  • ASXL1
  • BCOR
  • EZH2
  • SF3B1
  • SRSF2
  • STAG2
  • U2AF1
  • ZRSR2

Genetic changes are also becoming increasingly important in pediatric AML (pAML): Umeda et al. published a new genomic classification for categorizing pAML (Umeda et al. 2024).

AML: Diagnostic methods and their relevance

AML: MRD (Measurable Residual Disease)

Determination of MRD in AML serves as a prognostic/predictive biomarker for refined risk stratification and treatment decisions, as a monitoring tool for early detection of relapse, and as a potential endpoint in clinical trials. Highly sensitive quantitative detection methods (sensitivity 0.01-0.001%) are available for a variety of molecular genetic markers or fusion transcripts that are used to assess recurrence risk and eligibility for allogeneic stem cell transplantation. For example, for patients with mutated NPM1, RUNX1::RUNX1T1 fusion, CBFB::MYH11 fusion, or PML::RARA fusion, MRD determination by PCR is recommended (Heuser et al. 2021). MRD negativity represents a very favorable parameter for survival and low risk of recurrence (Schuurhuis et al. 2018, Freeman & Hourigan 2019, Rücker et al. 2019). Moreover, immunophenotyping (sensitivity 0.01%) now plays an increasingly important role in MRD determination and therapy stratification (Schuurhuis et al. 2018, Heuser et al. 2021). The FISH method can also be used in case of a positive marker, which cannot be monitored by PCR or LAIP. However, it is less sensitive (1-5%). NGS-based MRD diagnostics may also be useful for prognostic assessment. A detailed review on MRD in AML is available in European LeukemiaNet (ELN) guidelines by Heuser et al. and Döhner et al. (Heuser et al. 2021, Döhner et al. 2022) as well as in a recent review by Chea et al. (Chea et al. 2024).

AML: Prognosis

In addition to age, leukocyte count, and general health, karyotype and molecular genetic alterations represent important prognostic parameters and have a major impact on the therapeutic strategy. Modern genetic prognostic systems combine molecular mutations and cytogenetics (Grimwade et al. 2016, Döhner et al. 2022). An overview of the risk groups according to the European LeukemiaNet (ELN) classification can be found in Table 4.

Tab. 4: Genetic risk classification at initial diagnosis according to ELNa (Döhner et al. 2022)

Risk Category

Cyto- and molecular genetic abnormality


t(8;21)(q22;q22.1); RUNX1-RUNX1T1b,c
inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11b,c
Mutated NPM1b,d without FLT3-ITD
bZIP in-frame mutated CEBPAe


Mutated NPM1 b,d with FLT3-ITD
Wild-type NPM1 with FLT3-ITD
t(9;11)(p21.3;q23.3); KMT2A:: MLLT3 b,f
Cytogenetic and/or molecular abnormalities not classified as favorable or adverse


t(6;9)(p23;q34.1); DEK::NUP214
t(v;11q23.3); KMT2A-rearranged (exclusive KMT2A-PTD)
t(9;22)(q34.1;q11.2); BCR::ABL1

inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2::MECOM (EVI1)

-5 or del(5q); -7; -17/abnl(17p)
Complex karyotype g, monosomal karyotype h
Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 or ZRSR2i
Mutated TP53 j

a Frequencies, response rates and outcomes should be reported by risk category and, if sufficient, by specific genetic lesion.

b Mainly based on outcomes observed in intensively treated patients. Initial risk categorization may change over the course of treatment based on MRD measurements.

c Simultaneous presence of KIT and/or FLT3 mutations does not change the risk classification.

d AML with NPM1 mutation and cytogenetic abnormalities with unfavorable risk are categorized as unfavorable risk.

e The favorable prognosis for CEBPA mutation applies regardless of whether it is a monoallelic or biallelic mutation, as long as it is an in-frame mutation of the bZIP region.

f The presence of t(9;11)(p21.3;q23.3) takes precedence over rare, concomitant gene mutations with unfavorable risk.

g ≥ 3 independent aberrations in the absence of WHO-defined recurrent chromosomal aberrations; excludes hyperdiploid karyotypes with three or more trisomies (or polysomies) without structural abnormalities.

h two or more monosomies (except loss of the X or Y chromosome) or single monosomy in combination with at least one structural aberration (except in core-binding-factor (CBF) AML).

i currently, these markers should not be classified as unfavorable prognostic markers if they occur together with AML subtypes of the favorable risk group.

j TP53 mutation with a proportion of variant alleles of at least 10%, regardless of TP53 allele status (mono- or biallelic mutation); TP53 mutations are significantly associated with AML with complex and monosomal karyotypes.

AML: Therapy

Therapy options and algorithms can be found from the European LeukemiaNet (Döhner et al. 2022), the American Society of Hematology (Sekeres et al. 2020), the European Society of Medical Oncology (Heuser et al. 2020), and the Onkopedia website (Onkopedia Guideline AML) as well as from the National Comprehensive Cancer Center, among others.

Status: June 2024

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