Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

Academic Article

Abstract

  • 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 clonal remissions. In t-AML and elderly de novo AML populations, these alterations define a distinct genetic subtype that shares clinicopathologic properties with clinically confirmed s-AML and highlights a subset of patients with worse clinical outcomes, including a lower complete remission rate, more frequent reinduction, and decreased event-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00715637.
  • Authors

    Published In

  • Blood  Journal
  • Digital Object Identifier (doi)

    Author List

  • Lindsley RC; Mar BG; Mazzola E; Grauman PV; Shareef S; Allen SL; Pigneux A; Wetzler M; Stuart RK; Erba HP
  • Start Page

  • 1367
  • End Page

  • 1376
  • Volume

  • 125
  • Issue

  • 9