title: Recent advances in myelodysplastic syndromes: Molecular pathogenesis and its implications for targeted therapies.
abstract: Myelodysplastic syndromes (MDS) are defined as stem cell disorders caused by various gene abnormalities. Recent analysis using next-generation sequencing has provided great advances in identifying relationships between gene mutations and clinical phenotypes of MDS. Gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins and components of the cohesion complex participate in the pathogenesis and progression of MDS. Mutations in RNA splicing and DNA methylation occur early and are considered "founding mutations", whereas others that occur later are regarded as "subclonal mutations". RUNX1 mutations are more likely to subclonal; however, they apparently play a pivotal role in familial MDS. These genetic findings may lead to future therapies for MDS.
authors.affiliation: Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Harada
authors.forename: Yuka
authors.initials: Y
authors.lastname: Harada
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000473:pathology*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human
keywords: DNA methylation; RNA splicing; RUNX1; gene mutations; myelodysplastic syndromes