title: Genetic and epigenetic alterations of myeloproliferative disorders.
abstract: The classical BCR-ABL negative myeloproliferative neoplasms (MPN) polycythemia vera, essential thrombocythemia, and primary myelofibrosis are clonal hematopoietic disorders characterized by excessive production of terminally differentiated myeloid cells. In MPN patients, the disease can progress to secondary myelofibrosis or acute myeloid leukemia. Clonal hematopoiesis, disease phenotype, and progression are caused by somatically acquired genetic lesions of genes involved in cytokine signaling, RNA splicing, as well as epigenetic regulation. This review provides an overview of point mutations and cytogenetic lesions associated with MPN and addresses the role of these somatic lesions in MPN disease progression.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT25.3, 1090 Vienna, Austria.
authors.forename: Jelena D
authors.initials: JD
authors.lastname: Milosevic
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002869:Chromosome Aberrations; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D018450:Disease Progression; D044127:Epigenesis, Genetic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D012326:RNA Splicing; D053628:Receptors, Thrombopoietin / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C473949:ASXL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D053628:Receptors, Thrombopoietin; D012097:Repressor Proteins; C490778:SH2B3 protein, human; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; C541081:TET2 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D063151:Polycomb Repressive Complex 2; D050721:Proto-Oncogene Proteins c-cbl; D053614:Janus Kinase 2