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Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications

Stefan Fröhling, Claudia Scholl, D. Gary Gilliland, Ross L. Levine

From the Brigham and Women's Hospital; Howard Hughes Medical Institute, Harvard Medical School, Boston MA; and the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany

Address reprint requests to Stefan Fröhling, MD, or Ross L. Levine, MD, Brigham and Women's Hospital, Division of Hematology, Karp Family Research Building, 5th Floor, 1 Blackfan Cir, Boston, MA 02115; e-mail: sfrohling{at}rics.bwh.harvard.edu or rllevine{at}partners.org.

Myeloid malignancies are clonal disorders that are characterized by acquired somatic mutation in hematopoietic progenitors. Recent advances in our understanding of the genetic basis of myeloid malignancies have provided important insights into the pathogenesis of acute myeloid leukemia (AML) and myeloproliferative diseases (MPD) and have led to the development of novel therapeutic approaches. In this review, we describe our current state of understanding of the genetic basis of AML and MPD, with a specific focus on pathogenetic and therapeutic significance. Specific examples discussed include RAS mutations, KIT mutations, FLT3 mutations, and core binding factor rearrangements in AML, and JAK2 mutations in polycythemia vera, essential thrombocytosis, and chronic idiopathic myelofibrosis.

Supported in part by National Institutes of Health grants, the Howard Hughes Medical Institute, the Leukemia and Lymphoma Society, and the Doris Duke Charitable Foundation (D.G.G.). S.F. is supported by Grant No. FR 2113/1-1 from the Deutsche Forschungsgemeinschaft.

S.F. and C.S. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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