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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

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

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.

Comment in

PMID:
25550361
PMCID:
PMC4342352
DOI:
10.1182/blood-2014-11-610543
[Indexed for MEDLINE]
Free PMC Article

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