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Current Hematologic Malignancy Reports
Published in: Current Hematologic Malignancy Reports 5/2017

01-10-2017 | Myeloproliferative Neoplasms (B Stein, Section Editor)

Familial MPN Predisposition

Authors: Tsewang Tashi, Sabina Swierczek, Josef T. Prchal

Published in: Current Hematologic Malignancy Reports | Issue 5/2017

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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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Metadata
Title
Familial MPN Predisposition
Authors
Tsewang Tashi
Sabina Swierczek
Josef T. Prchal
Publication date
01-10-2017
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports / Issue 5/2017
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-017-0414-x

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