Association between JAK2 variable allele frequency and risk of thrombotic events in patients with myeloproliferative neoplasms.

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. Various studies have suggested that measuring the variable allele frequency (VAF) of JAK2 may provide useful insight regarding diagnosis, treatment, risks and outcomes in MPN patients. In particular, JAK2 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 VAF was associated with clinical outcomes in patients with MPN.

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

Results: We observed a significantly higher JAK2 VAF in PV and PMF versus ET. A significant association was observed between JAK2 VAF and risk of thrombotic events. When patients were stratified by thrombotic events prior to and post diagnosis, an association with JAK2 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 VAF is associated with thrombotic events post MPN diagnosis. JAK2 VAF may therefore provide a valuable prognostic indicator for risk of thrombosis in MPNs.