期刊
BLOOD
卷 115, 期 22, 页码 4517-4523出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-08-236448
关键词
-
类别
资金
- Wellcome Trust [07611]
- Leukaemia Research (United Kingdom) [0280]
- Cancer Research and Treatment Fund Inc, New York, NY
- Helmholtz Zentrum Munchen-German Research Center for Environmental Health
- German Federal Ministry of Education and Research
- State of Bavaria
- Italian Ministry of Health [ICS110.1/RF97.71]
- US National Institute on Aging [263 MD 9164, 263 MD 821336, N01-AG-1-1, N01-AG-1-2111]
- InCHIANTI
- National Institute on Aging, National Institutes of Health, Baltimore, MD
- Cancer Research UK [8961] Funding Source: researchfish
- Medical Research Council [G0300723B, G0300497] Funding Source: researchfish
- MRC [G0300497] Funding Source: UKRI
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 x 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. (Blood. 2010; 115(22): 4517-4523)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据