title: The molecular basis and clinical significance of genetic mutations identified in myelodysplastic syndromes.
abstract: Myelodysplastic syndromes (MDS) are a heterogeneous cluster of clonal hematopoietic neoplasms manifested by peripheral cytopenias, lineage dysplasia, and a predisposition to acute myeloid leukemia. The pathophysiology of MDS has not been well illustrated. Nevertheless, studies have implicated the MDS phenotype in a broad spectrum of genetic abnormalities. In addition to the known numerical and structural chromosomal abnormalities, with novel genomic sequencing technologies, approximately 80% of MDS patients have been shown to harbor somatic or acquired gene mutations. The mutations have been found to be related to RNA slicing, transcription regulation, DNA methylation, histone modification, DNA repair/tumor suppressor, signal transduction, and the cohesion complex. The clinical significance of the majority of genetic events has been validated based on a large cohort study that identified mutations as predictors for risk stratification in MDS patients and biomarkers for potential targeted therapies. In this review, we describe all novel key mutations in MDS and their significance in pathophysiology and clinical practice.
authors.affiliation: Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States. Electronic address: ling.zhang@moffitt.org.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hematologic Malignancies, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Padron
authors.affiliation: Department of Hematologic Malignancies, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lancet
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
keywords: Cohesion complex; DNA methylation/histone modification; DNA repair/tumor suppressor; Mutation; Myelodysplastic syndromes; Next generation sequencing; RNA slicing; Signal transduction; Transcription regulation