Acute myeloid leukemia ontogeny is defined by distinct somatic mutations.

Journal Article (Journal Article)

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 as #NCT00715637.

Full Text

Duke Authors

Cited Authors

  • Lindsley, RC; Mar, BG; Mazzola, E; Grauman, PV; Shareef, S; Allen, SL; Pigneux, A; Wetzler, M; Stuart, RK; Erba, HP; Damon, LE; Powell, BL; Lindeman, N; Steensma, DP; Wadleigh, M; DeAngelo, DJ; Neuberg, D; Stone, RM; Ebert, BL

Published Date

  • February 26, 2015

Published In

Volume / Issue

  • 125 / 9

Start / End Page

  • 1367 - 1376

PubMed ID

  • 25550361

Pubmed Central ID

  • PMC4342352

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2014-11-610543


  • eng

Conference Location

  • United States