title: After 10years of JAK2V617F: Disease biology and current management strategies in polycythaemia vera.
abstract: The JAK2V617F mutation accounts for the vast majority of patients with polycythaemia vera (PV) and around half of those with other Philadelphia-negative myeloproliferative neoplasms. Since its discovery in 2005, numerous insights have been gained into the pathways by which JAK2V617F causes myeloproliferation, including activation of JAK-STAT signalling but also through other canonical and non-canonical pathways. A variety of mechanisms explain how this one mutation can be associated with distinct clinical disorders, demonstrating how constitutional and acquired factors may interact in the presence of a single mutation to determine disease phenotype. Important biological questions remain unanswered in PV, in particular how JAK2V617F affects stem cell function and what mechanisms drive myelofibrotic and leukaemic transformation. Whilst current management is largely centred on prevention of cardiovascular events, future therapies must aim to target the JAK2-mutant clone, to reverse the underlying marrow pathology and to address the risk of transformation events.
authors.affiliation: Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Hills Rd, Cambridge CB2 0QQ, UK. Electronic address: jg738@cam.ac.uk.
authors.forename: Jacob
authors.initials: J
authors.lastname: Grinfeld
authors.affiliation: Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Hills Rd, Cambridge CB2 0QQ, UK. Electronic address: anna.godfrey1@nhs.net.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Godfrey
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019468:Disease Management; D005786:Gene Expression Regulation; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D015398:Signal Transduction
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Erythrocytosis; JAK2; Myeloproliferative; Polycythaemia vera