title: Disordered epigenetic regulation in the pathophysiology of myeloproliferative neoplasms.
abstract: The discovery of mutations activating JAK-STAT signaling in the majority of patients with myeloproliferative neoplasms (MPNs) led to identification of tyrosine kinase activation as the common predominant mechanism driving MPN pathogenesis. Nevertheless, the existence of additional genetic events that modify the MPN phenotype, predate JAK2 mutations, or contribute to leukemic transformation of MPNs was suspected. Recent advances in genomic technologies have led to the discovery of mutations in a number of epigenetic modifiers in patients with MPNs, including mutations in TET2, ASXL1, IDH1, IDH2, and EZH2. In addition to mutation, alterations in the expression or activity of chromatin-modifying/reading proteins PRMT5 and L3MBTL1 have been found to be important in MPN development. Moreover, the JAK2 mutation itself recently has been shown to directly affect histone post-translational modifications. This article reviews the clinical and functional implications of epigenetic alterations in the pathogenesis of MPNs.
authors.affiliation: Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center, 408 East 69th Street, New York, NY 10065, USA.
authors.forename: Su-Jiang
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Wahab
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D004789:Enzyme Activation; D044127:Epigenesis, Genetic / Q000235:genetics*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D009363:Neoplasm Proteins; D053614:Janus Kinase 2