title: Splice factor mutations and alternative splicing as drivers of hematopoietic malignancy.
abstract: Differential splicing contributes to the vast complexity of mRNA transcripts and protein isoforms that are necessary for cellular homeostasis and response to developmental cues and external signals. The hematopoietic system provides an exquisite example of this. Recently, discovery of mutations in components of the spliceosome in various hematopoietic malignancies (HMs) has led to an explosion in knowledge of the role of splicing and splice factors in HMs and other cancers. A better understanding of the mechanisms by which alternative splicing and aberrant splicing contributes to the leukemogenic process will enable more efficacious targeted approaches to tackle these often difficult to treat diseases. The clinical implications are only just starting to be realized with novel drug targets and therapeutic strategies open to exploitation for patient benefit.
authors.affiliation: Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia; Department of Molecular Pathology, SA Pathology, Adelaide, SA, Australia; School of Medicine, University of Adelaide, Adelaide, SA, Australia; Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Hahn
authors.forename: Parvathy
authors.initials: P
authors.lastname: Venugopal
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Hiwase
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D000068103:Serine-Arginine Splicing Factors; D000072668:Splicing Factor U2AF
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D017413:Ribonucleoprotein, U2 Small Nuclear; D012261:Ribonucleoproteins; C112491:SF3B1 protein, human; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors
keywords: alternative splicing; hematopoiesis; hematopoietic malignancy; leukemogenesis; splice factors