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Driver mutations in primary myelofibrosis and their implications

Szuber, Natasha; Tefferi, Ayalew

Current Opinion in Hematology: March 2018 - Volume 25 - Issue 2 - p 129–135
doi: 10.1097/MOH.0000000000000406
MYELOID DISEASE: Edited by Martin S. Tallman

Purpose of review Primary myelofibrosis (PMF) is one of the classic BCR-ABL1 negative myeloproliferative neoplasms (MPN). Oncogenic driver mutations in PMF include Janus kinase 2, calreticulin (CALR), and myeloproliferative leukemia virus oncogene. These mutations are not only pathogenetically relevant but might also influence disease outcome. Our objective for the current communication is to comprehensively review the distinct phenotypic, therapeutic, and prognostic implications of driver mutations in PMF.

Recent findings The discovery of driver mutations has revolutionized our understanding of pathogenic mechanisms and clinical heterogeneity in MPN, including PMF. Recently, there have been further advances in our knowledge of the molecular pathogenesis of MPN, particularly pertaining to CALR and its mutation. Moreover, the type and number of additional mutations, their order of acquisition, and their myriad combinatorial interactions with driver mutations may have dynamic pathogenic and clinical consequences. There are also additional data supporting the role of these genetic lesions and their associated allele burdens in modulating clinical features, including outcomes following treatment.

Summary Literature exists to support both phenotypic and prognostic correlates of conventional driver mutations in PMF. As the genetic landscape becomes increasingly complex, establishing the functional impact of these mutations and defining their interactions with other molecular, cytogenetic, and extrinsic factors will further our insight and potentially alter our clinical approach.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

Correspondence to Ayalew Tefferi, Division of Hematology, Department of Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. E-mail:

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