title: Spliceosomal gene mutations in myelodysplasia: molecular links to clonal abnormalities of hematopoiesis.
abstract: Genomic analyses of the myeloid malignancies and clonal disorders of hematopoiesis that may give rise to these disorders have identified that mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are among the most common targets of somatic mutations. These spliceosomal mutations often occur in a mutually exclusive manner with one another and, in aggregate, account for the most frequent class of mutations in patients with myelodysplastic syndromes (MDSs) in particular. Although substantial progress has been made in understanding the effects of several of these mutations on splicing and splice site recognition, functional connections linking the mechanistic changes in splicing induced by these mutations to the phenotypic consequences of clonal and aberrant hematopoiesis are not yet well defined. This review describes our current understanding of the mechanistic and biological effects of spliceosomal gene mutations in MDSs as well as the regulation of splicing throughout normal hematopoiesis.
authors.affiliation: Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
authors.forename: Daichi
authors.initials: D
authors.lastname: Inoue
authors.affiliation: Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
authors.forename: Robert K
authors.initials: RK
authors.lastname: Bradley
authors.affiliation: Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Wahab
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D006410:Hematopoiesis / Q000235:genetics*; D006801:Humans; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D012326:RNA Splicing; D017381:Spliceosomes / Q000235:genetics*
keywords: SF3B1; SRSF2; U2AF1; leukemia; mRNA splicing