JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms
JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms
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. 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
446-449
Jones, Amy V.
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Chase, Andrew
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Silver, Richard T.
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Oscier, David
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Zoi, Katerina
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Wang, Y. Lynn
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Cario, Holger
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Pahl, Heike L.
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Collins, Andrew
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Reiter, Andreas
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Grand, Francis
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Cross, Nicholas C.P.
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April 2009
Jones, Amy V.
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Chase, Andrew
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Silver, Richard T.
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Oscier, David
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Zoi, Katerina
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Wang, Y. Lynn
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Cario, Holger
b7c9019b-ee40-497d-936c-89f71c38bd8e
Pahl, Heike L.
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Collins, Andrew
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Reiter, Andreas
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Grand, Francis
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Cross, Nicholas C.P.
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Jones, Amy V., Chase, Andrew, Silver, Richard T., Oscier, David, Zoi, Katerina, Wang, Y. Lynn, Cario, Holger, Pahl, Heike L., Collins, Andrew, Reiter, Andreas, Grand, Francis and Cross, Nicholas C.P.
(2009)
JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms.
Nature Genetics, 41 (4), .
(doi:10.1038/ng.334).
Abstract
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. 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
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Published date: April 2009
Organisations:
Human Genetics
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Local EPrints ID: 69670
URI: http://eprints.soton.ac.uk/id/eprint/69670
ISSN: 1061-4036
PURE UUID: d1850896-a869-45a2-807e-7a7acc6f2594
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Date deposited: 27 Nov 2009
Last modified: 14 Mar 2024 02:46
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Author:
Amy V. Jones
Author:
Richard T. Silver
Author:
David Oscier
Author:
Katerina Zoi
Author:
Y. Lynn Wang
Author:
Holger Cario
Author:
Heike L. Pahl
Author:
Andreas Reiter
Author:
Francis Grand
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