Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early in leukemogenesis and often persist in…

• LA
  Leukemia and Lymphoma Society
• HC
  Harvard Catalyst
• EP
  Edward P. Evans Foundation
• LT
  Lady Tata Memorial Trust
• NI
  National Institutes of Health

  Awards: R01HL082945, P01 CA108631, T32GM007753
• NC
  National Cancer Institute

  Awards: T32GM007753, R01HL082945
• NI
  National Institute of General Medical Sciences

  Award: T32GM007753