JAK2 V617F mutation in MPN pathogenesis: Insights and potential therapeutic implications

The JAK2^V617F mutation is a common driver mutation in MPN and leads to persistent activation of the JAK/STAT signaling pathway, which is pivotal in promoting cell proliferation, differentiation, and anti-apoptosis.¹ Whilst JAK inhibitors are widely used in clinical practice for the treatment of MPN, they are not curative and therefore require long‐term treatment; which is associated with serious physical, psychological and economical burdens for patients.¹

Easing the long‐term treatment burden and potentially curing MPN will require a detailed understanding of its pathogenesis in order to elucidate new therapeutic targets and combination therapy strategies.¹ Zhang et al.¹explored the roles of the JAK2^V617F mutation in MPN, including mechanisms of non‐JAK/STAT pathways, cellular methylation regulation, accumulation of DNA damage, and cardiovascular effects, with a view to informing combination therapy options for MPN. We summarize key findings from their review recently published in Cancer.¹