Association between JAK2V617F variable allele frequency and risk of thrombotic events in patients with myeloproliferative neoplasms.

Abstract

Background: Myeloproliferative neoplasms (MPNs) are a group of chronic disorders of the bone marrow characterised by the overproduction of clonal myeloid stem cells. The most common driver mutation found in MPNs is a point mutation on exon 14 of the JAK2 gene, JAK2^V617F. Various studies have suggested that measuring the variable allele frequency (VAF) of JAK2^V617F may provide useful insight regarding diagnosis, treatment, risks and outcomes in MPN patients. In particular, JAK2^V617F has been associated with increased risk of thrombotic events, a leading cause of mortality in MPNs.

Aims: The aim of this study was to determine if JAK2^V617F VAF was associated with clinical outcomes in patients with MPN.

Methods: JAK2^V617F VAF was determined by quantitative PCR (qPCR) in a cohort of 159 newly diagnosed MPN patients, and the association of JAK2^V617F VAF and risk of thrombosis was examined in this cohort.

Results: We observed a significantly higher JAK2^V617F VAF in PV and PMF versus ET. A significant association was observed between JAK2^V617F VAF and risk of thrombotic events. When patients were stratified by thrombotic events prior to and post diagnosis, an association with JAK2^V617F VAF was only observed with post diagnosis thrombotic events. Of note, these associations were not observed when looking at each MPN subtype in isolation.

Conclusions: We have shown that a higher JAK2^V617F VAF is associated with thrombotic events post MPN diagnosis. JAK2^V617F VAF may therefore provide a valuable prognostic indicator for risk of thrombosis in MPNs.