The JAK2 46/1 haplotype confers susceptibility to essential thrombocythemia regardless of JAK2V617F mutational status-clinical correlates in a study of 226 consecutive patients.

The germline JAK2 haplotype 46/1, tagged by the 'C' allele of single-nucleotide polymorphism (SNP) rs12343867 (C/T), has been associated with JAK2V617F (VF)-positive myeloproliferative neoplasms. SNP rs12343867 was genotyped using bone marrow DNA in 226 consecutive patients with essential thrombocythemia (ET) with concomitant analysis of VF allele burden. The incidence of the 46/1-linked C allele was significantly higher in ET (genotype: CC 15%, CT 52%, TT 33%; C-allele frequency: 41%) than in population controls (P<0.01). Genotype distributions were similar among VF-positive/VF-negative patients (genotype: CC 18/11%, CT 52/53%, TT 30/36%; C-allele: 44/38%; P=0.29). Haplotype 46/1 frequency was remarkably similar when comparing VF-negative patients to those with <10% VF allele burden, but significantly higher in the presence of >10% VF allele burden (genotype: CC 11/13/38%, CT 53/56/38%, TT 36/31/24%; C-allele frequency: 38/41/57%; P<0.01). The clinical features of 46/1-positive and -negative ET were indistinguishable, including blood counts, rate of thrombosis/disease transformation and survival. We conclude that JAK2 haplotype 46/1 confers susceptibility to developing ET independent of VF mutational status and does not seem to further affect the clinical phenotype or prognosis.