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Blood. 2015 Feb 26;125(9):1367-76. doi: 10.1182/blood-2014-11-610543. Epub 2014 Dec 30.

Acute myeloid leukemia ontogeny is defined by distinct somatic mutations.

Author information

  • 1Department of Medical Oncology, Division of Hematological Malignancies.
  • 2Department of Pediatric Oncology, and.
  • 3Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston MA;
  • 4Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
  • 5Hofstra North Shore-LIJ School of Medicine, Hempstead, NY;
  • 6Hôpital Haut-Leveque, Centre Hospitalier Universitaire Bordeaux, Pessac, France;
  • 7Roswell Park Cancer Institute, Buffalo, NY;
  • 8Hollings Cancer Center, Medical University of South Carolina, Charleston, SC;
  • 9Division of Hematology and Oncology, University of Alabama, Birmingham, Birmingham, AL;
  • 10Helen Diller Family Comprehensive Cancer Center, The University of California, San Francisco, CA;
  • 11Comprehensive Cancer Center of Wake Forest University, Winston Salem, NC; and.
  • 12Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.


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.

© 2015 by The American Society of Hematology.

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