Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy arising from clonal expansion of myeloid progenitor cells with arrested differentiation, resulting in accumulation of immature myeloid blasts (>=20% of marrow cellularity) that suppress normal hematopoiesis. Median age at diagnosis is 68 years, with annual incidence of 4 per 100,000. Risk factors include prior chemotherapy/radiotherapy (therapy-related AML), antecedent myelodysplastic syndrome or myeloproliferative neoplasm, benzene exposure, ionizing radiation, smoking, and inherited syndromes (Fanconi anemia, Down syndrome, germline DDX41/CEBPA mutations).
WHO 2022 classification recognizes AML with defining genetic abnormalities (RUNX1::RUNX1T1, CBFB::MYH11, PML::RARA t(15;17), KMT2A rearrangements, NPM1, CEBPA bZIP, MECOM, BCR::ABL1), AML with myelodysplasia-related changes (mutations in ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2; or specific cytogenetics), and AML defined by differentiation. ELN 2022 risk stratification: favorable (NPM1+ without FLT3-ITD, biallelic CEBPA bZIP, t(8;21), inv(16)), intermediate (FLT3-ITD with NPM1+, KMT2A non-MLLT3), adverse (TP53, complex karyotype, monosomal karyotype, MECOM rearrangement, ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2 mutations).
Treatment is risk-adapted: fit younger patients receive intensive induction chemotherapy (7+3 regimen: cytarabine 100-200 mg/m2 continuous infusion x7 days + daunorubicin 60-90 mg/m2 or idarubicin 12 mg/m2 x3 days), with targeted additions (midostaurin for FLT3-mutated AML, gemtuzumab ozogamicin for CD33+ favorable-risk, glasdegib for older patients). Post-remission therapy includes consolidation with high-dose cytarabine for favorable-risk and allogeneic stem cell transplantation for intermediate/adverse-risk in first remission. Older/unfit patients receive azacitidine plus venetoclax (response rate ~67%, median survival 14.7 months in VIALE-A trial), or low-dose cytarabine plus venetoclax. Targeted therapies include gilteritinib for relapsed FLT3-mutated AML, ivosidenib/olutasidenib for IDH1, enasidenib for IDH2 mutations. Acute promyelocytic leukemia (APL, PML::RARA) is treated with all-trans retinoic acid (ATRA) plus arsenic trioxide, achieving >95% cure rates.