Development of a reliable PCR-RFLP assay for investigation of the JAK2 rs10974944 SNP, which might predispose to the acquisition of somatic mutation JAK2(V617F).

摘要

Polycythemia vera, essential thrombocythemia and primary myelofibrosis are the 3 classical myeloprolifera-tive neoplasms (MPNs), negative for the BCR-ABL fu sion. Their molecular physiopathology remained obscure for decades, until several research groups reported in 2005 that a single somatic point mutation in the gene cod ing for Janus-kinase 2 (JAK2), predicting a valine-to-phe-nylalanine substitution in position 617 (JAK2~(V617F)), char acterize most of polycythemia vera and about half of es sential thrombocythemia and primary myelofibrosis patients [1-5]. JAK2~(V617F) mutation leads to constitutive activation of the JAK-STAT signaling pathway and thus continuous proliferation of the myeloid precursors [1-5]. Further studies indicated, however, that this mutation might not be the primary molecular event in these dis eases [6, 7]. Very recently, 3 independent research groups reported for the first time that the JAK2~(V617F) tends to oc cur, or could have a selective advantage, in a specific JAK2 haplotype [8-10]. The common point of the 3 reports was a single nucleotide polymorphism (SNP) within the JAK2 gene, called rsl0974944, part of the putative JAK2~(V617F)-predisposing haplotype, of which the C allele is the com mon allele, whereas the G allele is the variant.