<i><scp>TERT</scp></i> rs2736100 A&gt;C <scp>SNP</scp> and <i><scp>JAK</scp>2</i> 46/1 haplotype significantly contribute to the occurrence of <i><scp>JAK</scp>2</i> V617F and <i><scp>CALR</scp></i> mutated myeloproliferative neoplasms – a multicentric study on 529 patients

Abstract

Polycythaemia vera ( PV ), essential thrombocythaemia ( ET ) and primary myelofibrosis ( PMF ) represent typical myeloproliferative neoplasms ( MPN ), usually characterized by specific somatic driver mutations ( JAK 2 V617F, CALR and MPL ). JAK 2 46/1 haplotype and telomerase reverse transcriptase gene ( TERT ) rs2736100 A&gt;C single nucleotide polymorphism ( SNP ) could represent a large fraction of the genetic predisposition seen in MPN . The rs10974944 C&gt;G SNP , tagging the JAK 2 46/1 haplotype, and the TERT rs2736100 A&gt;C SNP were genotyped in 529 MPN patients with known JAK 2 V617F, CALR and MPL status, and 433 controls. JAK 2 46/1 haplotype strongly correlated to JAK 2 V617F‐positive MPN and, to a lesser extent, CALR ‐positive MPN . The TERT rs2736100 A&gt;C SNP strongly correlated to all MPN , regardless of the phenotype ( PV , ET or PMF ) and major molecular subtype ( JAK 2 V617F‐ or CALR ‐positive). While both variants have a significant contribution, they have nuanced consequences, with JAK 2 46/1 predisposing essentially to JAK 2 V617F‐positive MPN , and TERT rs2736100 A&gt;C having a more general, non‐specific effect on all MPN , regardless of phenotype or major molecular subtype.