title: Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal.
abstract: JAK2 and MPL mutations are recurrent in myeloproliferative neoplasms (MPNs). A JAK2 mutation, primarily JAK2V617F, is almost invariably associated with polycythemia vera (PV). However, JAK2V617F also occurs in the majority of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) as well as in a much smaller percentage of those with other MPNs. The mechanism(s) behind this one allele-multiple phenotypes phenomenon has not been fully elucidated. The issue is further confounded by the presence of marked variation in JAK2V617F allele burden among mutation-positive patients. In the current communication, we discuss potential mechanisms for phenotypic diversity among JAK2V617F-positive MPNs as well as review the current literature in regard to genotype-phenotype correlations (that is clinical correlates and prognostic significance) in the context of both the presence or absence of the mutation (ET and PMF) and its allele burden (PV, ET and PMF).
authors.affiliation: UF di Ematologia, Dipartimento di Area Critica Medico-Chirurgica, Università degli Studi, Azienda Ospedaliera-Universitaria Careggi, Firenze, Italy. amvannucchi@unifi.it
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: E
authors.initials: E
authors.lastname: Antonioli
authors.forename: P
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: A
authors.initials: A
authors.lastname: Pardanani
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000483:Alleles; D018952:Antigens, CD34 / Q000032:analysis; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D010641:Phenotype; D011087:Polycythemia Vera / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; C507924:JAK2 protein, human; D053614:Janus Kinase 2