TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms - a multicentric study on 529 patients.

Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F-positive MPN and, to a lesser extent, CALR-positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F- or CALR-positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F-positive MPN, and TERT rs2736100 A>C having a more general, non-specific effect on all MPN, regardless of phenotype or major molecular subtype.