Myeloproliferative Neoplasms

Myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis, are a heterogenous collection of myeloid stem cell disorders. Three phenotype driver mutations in JAK2, CALR and MPL are identified in most patients and underlie the molecular pathogenesis through JAK2-STAT hyperactivation. The occurrence of co-operating mutations facilitates the clonal evolution and impacts the clinical phenotype and prognostic outcome across disease spectrum. Chronic inflammation reinforces the expansion of malignant clones and accelerates myelofibrosis development. New generations of JAK2 inhibitors, combinational therapy and investigational agents show promising data in pre-clinical experiments. This chapter provides a comprehensive overview on intrinsic and extrinsic mechanisms of MPN pathogenesis and highlights the potential therapeutic targets for future investigation.