title: Splicing factor gene mutations in hematologic malignancies.
abstract: Alternative splicing generates a diversity of messenger RNA (mRNA) transcripts from a single mRNA precursor and contributes to the complexity of our proteome. Splicing is perturbed by a variety of mechanisms in cancer. Recurrent mutations in splicing factors have emerged as a hallmark of several hematologic malignancies. Splicing factor mutations tend to occur in the founding clone of myeloid cancers, and these mutations have recently been identified in blood cells from normal, healthy elderly individuals with clonal hematopoiesis who are at increased risk of subsequently developing a hematopoietic malignancy, suggesting that these mutations contribute to disease initiation. Splicing factor mutations change the pattern of splicing in primary patient and mouse hematopoietic cells and alter hematopoietic differentiation and maturation in animal models. Recent developments in this field are reviewed here, with an emphasis on the clinical consequences of splicing factor mutations, mechanistic insights from animal models, and implications for development of novel therapies targeting the precursor mRNA splicing pathway.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA.|Center for Applied Medical Research, University of Navarra, Spain; and.
authors.forename: Borja
authors.identifier: 0000-0001-7908-7089
authors.initials: B
authors.lastname: Saez
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Matthew J
authors.identifier: 0000-0002-7753-1091
authors.initials: MJ
authors.lastname: Walter
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA.
authors.forename: Timothy A
authors.identifier: 0000-0002-7710-1171
authors.initials: TA
authors.lastname: Graubert
mesh_terms: D000818:Animals; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D009154:Mutation; D000072260:RNA Splicing Factors / Q000235:genetics*
chemical_list: D000072260:RNA Splicing Factors