The Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) are a heterogenous group of hematopoietic stem cell diseases characterized by activated JAK/STAT signaling and a variable propensity toward myelofibrotic and leukemic transformation. Acquisition of somatic mutations in addition to the canonical JAK2, MPL, and CALR mutations found in MPNs is an important catalyst in the clonal evolution and progression of these disorders. In recent years, our increasing understanding of the molecular landscape of Ph- MPNs has generated important prognostic information that informs our approach to risk stratification and therapeutic decision-making. This review will focus on the critical impact of genomics on our approach to management of advanced Ph- MPNs.
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