The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms.

Autor: Soler G; Hematology and Medical Oncology Unit, Hospital Universitario Morales-Meseguer, Centro Regional de Hemodonacion, IMIB-Arrixaca, C/Ronda de Garay, sn. 3003, Murcia, Spain., Bernal-Vicente A, Antón AI, Torregrosa JM, Caparrós-Pérez E, Sánchez-Serrano I, Martínez-Pérez A, Sánchez-Vega B, Vicente V, Ferrer-Marin F
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2015 May; Vol. 94 (5), pp. 789-94. Date of Electronic Publication: 2014 Dec 09.
DOI: 10.1007/s00277-014-2266-y
Abstrakt: Somatic mutations in the CALR gene were recently discovered in a substantial proportion of Philadelphia-negative chronic myeloproliferative neoplasm (cMPN) patients lacking JAK2 and MPL mutations. Somatically acquired defects are not the only pathogenic mechanism involved in these disorders. Since germline JAK2 46/1 haplotype predisposes to cMPN-associated mutations, including JAK2V617F and MPLW515K7L, we evaluated whether the 46/1 haplotype also confers susceptibility to CALR-mutated cMPN, both in sporadic and familial cases. The single-nucleotide polymorphism rs10974944, which tags 46/1, was investigated in 155 sporadic MPN patients and 270 unrelated controls, as well as in 11 familial cMPN cases and 36 unaffected relative controls. As described elsewhere, the 46/1 haplotype was overrepresented, both in sporadic and familial cMPN. In sporadic cMPN, the JAK2 46/1 haplotype was closely associated with JAK2V617F (p = 0.0003) but not with JAK2-nonmutated cases. Analysis of CALR-mutated sporadic cMPN (n = 22) showed no association between CALR mutations and 46/1 haplotype (p = 0.87). Regarding the familial cMPN, the prevalence of carriers of the G allele was higher in familial (81.8%) than in sporadic (62%) cMPN, but it did not differ significantly (p = 0.3). Although we described a family with carriers of both JAK2V617F and CALR mutations, due to the low number of CALR-mutated familial cases, we could not determinate whether the JAK2 46/1 haplotype predisposes or does not to CALR-mutated familial cMPN. We conclude, for the first time, that the 46/1 haplotype, unlike JAK2V617F and MPLW515K7L, is not associated with CALR-mutated cMPN.
Databáze: MEDLINE
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