title: Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations.
abstract: During the past 10 years, major progress has been accomplished with the discovery of activating mutations that are associated with the vast majority of BCR-ABL negative human myeloproliferative neoplasms (MPNs). The identification in 2005 of JAK2 V617F triggered great interest in the JAK2-STAT5/STAT3 pathway. Discovery in 2006 of mutants of thrombopoietin receptor (TPO-R/MPL) and later on of mutants in negative regulators of JAK-STAT pathway led to the notion that persistent JAK2 activation is a hallmark of MPNs. In 2013, mutations in the gene coding for the chaperone calreticulin were reported in 20-30% of essential thrombocythemia and primary myelofibrosis patients. Here, we will address the question: what do we know about calreticulin that could help us understand its role in MPNs? In addition to oncogenic driver mutations, certain MPNs also exhibit epigenetic mutations. Targeting of both oncogenic drivers and epigenetic defects could be required for effective therapy.
authors.affiliation: Ludwig Institute for Cancer Research, Avenue Hippocrate 74, UCL 75-4, Brussels, B1200, Belgium.|de Duve Institute, Université catholique de Louvain, Brussels, B1200, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cahu
authors.affiliation: Ludwig Institute for Cancer Research, Avenue Hippocrate 74, UCL 75-4, Brussels, B1200, Belgium. stefan.constantinescu@bru.licr.org.|de Duve Institute, Université catholique de Louvain, Brussels, B1200, Belgium. stefan.constantinescu@bru.licr.org.
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Constantinescu
mesh_terms: D037282:Calreticulin / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Calreticulin; JAK2V617F; Myeloproliferative neoplasms; TPO-R