The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms

Jones, Amy V., Campbell, Peter J., Beer, Philip A., Schnittger, Susanne, Vannucchi, Alessandro M., Zoi, Katerina, Percy, Melanie J., McMullin, Mary Frances, Scott, Linda M., Tapper, William, Silver, Richard T., Oscier, David, Harrison, Claire N., Grallert, Harald, Kisialiou, Aliaksei, Strike, Paul, Chase, Andrew J., Green, Anthony R. and Cross, Nicholas C. P. (2010) The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. Blood, 115 22: 4517-4523. doi:10.1182/blood-2009-08-236448

Author Jones, Amy V.
Campbell, Peter J.
Beer, Philip A.
Schnittger, Susanne
Vannucchi, Alessandro M.
Zoi, Katerina
Percy, Melanie J.
McMullin, Mary Frances
Scott, Linda M.
Tapper, William
Silver, Richard T.
Oscier, David
Harrison, Claire N.
Grallert, Harald
Kisialiou, Aliaksei
Strike, Paul
Chase, Andrew J.
Green, Anthony R.
Cross, Nicholas C. P.
Title The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms
Formatted title
The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2010-06
Sub-type Article (original research)
DOI 10.1182/blood-2009-08-236448
Volume 115
Issue 22
Start page 4517
End page 4523
Total pages 7
Place of publication Washington, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
The 46/1 JAK2 haplotype predisposes to V617F-positive myeloproliferative neoplasms, but the underlying mechanism is obscure. We analyzed essential thrombocythemia patients entered into the PT-1 studies and, as expected, found that 46/1 was overrepresented in V617F-positive cases (n = 404) versus controls (n = 1492, P = 3.9 × 10−11). The 46/1 haplotype was also overrepresented in cases without V617F (n = 347, P = .009), with an excess seen for both MPL exon 10 mutated and V617F, MPL exon 10 nonmutated cases. Analysis of further MPL-positive, V617F-negative cases confirmed an excess of 46/1 (n = 176, P = .002), but no association between MPL mutations and MPL haplotype was seen. An excess of 46/1 was also seen in JAK2 exon 12 mutated cases (n = 69, P = .002), and these mutations preferentially arose on the 46/1 chromosome (P = .029). No association between 46/1 and clinical or laboratory features was seen in the PT-1 cohort either with or without V617F. The excess of 46/1 in JAK2 exon 12 cases is compatible with both the “hypermutability” and “fertile ground” hypotheses, but the excess in MPL-mutated cases argues against the former. No difference in sequence, splicing, or expression of JAK2 was found on 46/1 compared with other haplotypes, suggesting that any functional difference of JAK2 on 46/1, if it exists, must be relatively subtle.
Keyword Familial polycythemia-vera
Genome-wide association
Essential thrombocythemia
Confers susceptibility
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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