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 post cytotoxic 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 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