Pathogenesis and management of high molecular risk myeloproliferative neoplasms

Classical myeloproliferative neoplasms (MPN) are clonal stem cell disorders characterized by driver mutations that affect the constitutive activation of JAK-signaling. Mutations additional to an MPN-driver occur in a large number of patients and have been shown be associated with disease presentation and progression. In this review, we outline the current hypotheses regarding how clonal evolution in MPN is thought to occur and the functional mechanisms as to how concomitant somatic mutations (i.e., mutations in genes other than the 'driver' genes) contribute to disease progression. We discuss the definitions of high molecular risk MPN, provide an overview of how concomitant mutations influence the clinical management of MPN and suggest how the rapidly developing genetic risk stratification can be utilized to improve clinical outcomes.