JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms

被引：311

作者：

Jones, Amy V. ^{[1
,2
]}

Chase, Andrew ^{[1
,2
]}

Silver, Richard T. ^{[3
]}

Oscier, David ^{[4
]}

Zoi, Katerina ^{[5
]}

Wang, Y. Lynn ^{[3
]}

Cario, Holger ^{[6
]}

Pahl, Heike L. ^{[7
]}

Collins, Andrew ^{[2
]}

Reiter, Andreas ^{[8
]}

Grand, Francis ^{[1
,2
]}

Cross, Nicholas C. P. ^{[1
,2
]}

机构：

[1] Wessex Reg Genet Lab, Salisbury, Wilts, England

[2] Univ Southampton, Div Human Genet, Southampton SO9 5NH, Hants, England

[3] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[4] Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England

[5] Acad Athens, Biomed Res Fdn, Haematol Res Lab, Athens, Greece

[6] Univ Hosp Ulm, Dept Pediat & Adolescent Med, Ulm, Germany

[7] Univ Hosp Freiburg, Dept Expt Anaesthesiol, Freiburg, Germany

[8] Univ Heidelberg, Fak Klin Med Mannheim, Med Univ Klin 3, D-6900 Heidelberg, Germany

来源：

NATURE GENETICS | 2009年 / 41卷 / 04期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; SUSCEPTIBILITY LOCI; ESSENTIAL THROMBOCYTHEMIA; CANCER SUSCEPTIBILITY; ACTIVATING MUTATION; MYELOID METAPLASIA; DISORDERS; MYELOFIBROSIS;

D O I：

10.1038/ng.334

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Chronic myeloproliferative neoplasms (MPNs) are a group of related conditions characterized by the overproduction of cells from one or more myeloid lineages. More than 95% of cases of polycythemia vera, and roughly half of essential thrombocythemia and primary myelofibrosis acquire a unique somatic 1849G> T JAK2 mutation (encoding V617F) that is believed to be a critical driver of excess proliferation(1-4). We report here that JAK2(V617F)-associated disease is strongly associated with a specific constitutional JAK2 haplotype, designated 46/1, in all three disease entities compared to healthy controls ( polycythemia vera, n = 192, P = 2.9 x 10(-16); essential thrombocythemia, n 78, P = 8.2 x 10(-9) and myelofibrosis, n = 41, P = 8.0 x 10(-5)). Furthermore, JAK2(V617F) specifically arises on the 46/1 allele in most cases. The 46/1 JAK2 haplotype thus predisposes to the development of JAK2(V617F)-associated MPNs (OR 3.7; 95% CI = 3.1-4.3) and provides a model whereby a constitutional genetic factor is associated with an increased risk of acquiring a specific somatic mutation.

引用

页码：446 / 449

页数：4

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