Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Blood, 2010-06, Vol.115 (22), p.4517-4523

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2010

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• 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.