Mutations in spliceosome genes and therapeutic opportunities in myeloid malignancies Review
| Authors: | Taylor, J.; Lee, S. C. |
| Review Title: | Mutations in spliceosome genes and therapeutic opportunities in myeloid malignancies |
| Abstract: | Since the discovery of RNA splicing more than 40 years ago, our comprehension of the molecular events orchestrating constitutive and alternative splicing has greatly improved. Dysregulation of pre-mRNA splicing has been observed in many human diseases including neurodegenerative diseases and cancer. The recent identification of frequent somatic mutations in core components of the spliceosome in myeloid malignancies and functional analysis using model systems has advanced our knowledge of how splicing alterations contribute to disease pathogenesis. In this review, we summarize our current understanding on the mechanisms of how mutant splicing factors impact splicing and the resulting functional and pathophysiological consequences. We also review recent advances to develop novel therapeutic approaches targeting splicing catalysis and splicing regulatory proteins, and discuss emerging technologies using oligonucleotide-based therapies to modulate pathogenically spliced isoforms. © 2019 The Authors. Genes, Chromosomes & Cancer published by Wiley Periodicals, Inc. |
| Keywords: | gene mutation; somatic mutation; review; nonhuman; gene; gene targeting; rna binding protein; sulfonamide; hematopoiesis; catalysis; spliceosome; oligonucleotide; rna splicing; regulator protein; molecular pathology; myeloid leukemia; human; priority journal; sf3b1; sf3b1 gene; srsf2; u2af1; srsf2 gene; u2af1 gene; rna isoform; zrsr2 gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 58 |
| Issue: | 12 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2019-12-01 |
| Start Page: | 889 |
| End Page: | 902 |
| Language: | English |
| DOI: | 10.1002/gcc.22784 |
| PUBMED: | 31334570 |
| PROVIDER: | scopus |
| PMCID: | PMC6852509 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 November 2019 -- Source: Scopus |
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