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Familial MPN Predisposition

  • Myeloproliferative Neoplasms (B Stein, Section Editor)
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Abstract

Chronic myeloproliferative neoplasms (MPN) characteristically arise from a somatic mutation in the pluripotent hematopoietic stem cell, and most common recurring mutations are in the JAK2, CALR, and cMPL genes. However, these mutations are not founder mutations, but mainly drive the disease phenotype and a pre-existing germline predisposition has been long speculated, but has not been clearly defined to date. Genome-wide association studies in family clusters of MPN have identified a number of genetic variants that are associated with increased germline risk for developing clonal MPN. The strongest association discovered so far is the presence of JAK2 46/1 haplotype, and subsequently, many studies have found additional variants in other genes, most notably in TERT gene. However, these still account for a small fraction of familial MPN, and more in-depth studies including whole genome sequencing are needed to gain better insight into familial genetic predisposition of clonal MPNs.

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Authors and Affiliations

  1. Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT, USA

    Tsewang Tashi, Sabina Swierczek & Josef T. Prchal

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  1. Tsewang Tashi
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  2. Sabina Swierczek
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Correspondence to Josef T. Prchal.

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Tsewang Tashi, Sabina Swierczek, and Josef Prchal each declare no potential conflicts of interest.

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This article contains no studies with human or animal subjects performed by any of the authors.

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Tsewang Tashi and Sabina Swierczek have equal credit to this study.

This article is part of the Topical Collection on Myeloproliferative Neoplasms

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Tashi, T., Swierczek, S. & Prchal, J.T. Familial MPN Predisposition. Curr Hematol Malig Rep 12, 442–447 (2017). https://doi.org/10.1007/s11899-017-0414-x

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