title: Pathogenesis of myeloproliferative neoplasms.
abstract: Major progress has been recently made in understanding the molecular pathogenesis of myeloproliferative neoplasms (MPN). Mutations in one of four genes-JAK2, MPL, CALR, and CSF3R-can be found in the vast majority of patients with MPN and represent driver mutations that can induce the MPN phenotype. Hyperactive JAK/STAT signaling appears to be the common denominator of MPN, even in patients with CALR mutations and the so-called "triple-negative" MPN, where the driver gene mutation is still unknown. Mutations in epigenetic regulators, transcription factors, and signaling components modify the course of the disease and can contribute to disease initiation and/or progression. The central role of JAK2 in MPN allowed development of small molecular inhibitors that are in clinical use and are active in almost all patients with MPN. Advances in understanding the mechanism of JAK2 activation open new perspectives of developing the next generation of inhibitors that will be selective for the mutated forms of JAK2.
authors.affiliation: Department of Biomedicine, Experimental Hematology, University Hospital Basel, Basel, Switzerland. Electronic address: radek.skoda@unibas.ch.
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
authors.affiliation: Hematology Institute, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
authors.forename: Adrian
authors.initials: A
authors.lastname: Duek
authors.affiliation: Department of Biomedicine, Experimental Hematology, University Hospital Basel, Basel, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Grisouard
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins