Leukemia, Acute Myeloid

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DESCRIPTION

  • Acute myeloid leukemia (AML) is characterized by proliferation of abnormal immature myeloid progenitors (blasts) with reduced capacity to differentiate leading to bone marrow failure and a variety of systemic symptoms.
  • Historically, the French–American–British (FAB) classification system divided AML based on the cell morphology with the addition of cytogenetics (subtypes M0 to M7).
  • The World Health Organization (WHO) classifications attempt to provide more meaningful prognostic information.
    • AML with defining genetic abnormalities:
      • Translocation in t(8;21) RUNX1::RUNX1T1 fusion, t(9;11) KMT2A, t(6;9) DEK::NUP214, t(1;22) RBM15::MRTFA, t(15;17) APL with PML::RARA fusion
      • Inversion in chromosome 16 inv(16) CBFB::MYH11, inv(3) MECOM
      • Other defined genetic alterations
    • AML, myelodysplasia related: presence of a prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) that transformed into AML
    • Myeloid neoplasms postcytotoxic therapy: AML, MDS, and MDS/MPN exposed to cytotoxic therapy
    • Myeloid neoplasms associated with germline predisposition: Down syndrome, Fanconi anemia, RASopathies
    • Acute leukemias of mixed or ambiguous lineage (biphenotypic acute leukemia)
    • Myeloid sarcoma

EPIDEMIOLOGY

  • New cases in men and women is 4.1 per 100,000 men and women per year.
  • Male ≥ female

Incidence

The incidence of AML increases with age, and median age is 67 years.

Prevalence

~20,050 cases estimated in 2022 making it the most common type of leukemia in adults

ETIOLOGY AND PATHOPHYSIOLOGY

Genetics

  • Three risk groups
    • Good risk: inv(16), t(8;21), t(15;17)
    • Standard risk: normal karyotype
    • Poor risk: monosomy 5 and 7 (typically secondary AML), deletion 5q, abnormalities of 11q23, or complex karyotype
  • FLT3 gene mutations, especially internal tandem duplications (FLT3-ITD), have been associated with poor survival in AML. These and growing list of (onco)gene (e.g., NPM1, IDH1/2, DNMT3A, and P53) mutations have been studied to further risk-stratify patients (1).

RISK FACTORS

  • Genetic predisposition (e.g., Down syndrome); Bloom syndrome (~25% develop AML), Fanconi anemia (52%), neurofibromatosis, Li-Fraumeni syndrome, Wiskott-Aldrich syndrome, Kostmann syndrome, and Diamond-Blackfan anemia
  • Radiation exposure
  • Immunodeficiency states
  • Chemical and drug exposure (nitrogen mustard and alkylating agents; benzene)
  • MDS
  • Cigarette smoking

GENERAL PREVENTION

Treatment of high-risk MDS with hypomethylating agents (5-azacitidine [Vidaza]) may prolong time to transformation from MDS into AML

COMMONLY ASSOCIATED CONDITIONS

  • Disseminated intravascular coagulopathy (DIC) especially in acute promyelocytic leukemia (APL) but may be seen in any AML
  • Leukostasis (high blast number and increased adhesive ability of blasts)
  • Tumor lysis syndrome (TLS): spontaneous or in response to chemotherapy

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