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Clinical and functional studies over the past 10 y have confirmed that mutations in RNA splicing factors are among the most recurrent genetic abnormalities in hematologic neoplasms, including myeloid malignancies, chronic lymphocytic leukemia, mantle cell lymphoma, and clonal hematopoiesis. These findings indicate an important role for splicing factor mutations in the development of clonal hematopoietic disorders. Mutations in core or accessory components of the RNA spliceosome complex alter splicing sites in a manner of change of function. These changes can result in the dysregulation of cancer-associated gene expression and the generation of novel mRNA transcripts, some of which are not only critical to disease development but may be also serving as potential therapeutic targets. Furthermore, multiple studies have revealed that hematopoietic cells bearing mutations in splicing factors depend on the expression of the residual wild-type allele for survival, and these cells are more sensitive to reduced expression of wild-type splicing factors or chemical perturbations of the splicing machinery. These findings suggest a promising possibility for developing novel therapeutic opportunities in tumor cells based on mutations in splicing factors. Here, we combine current knowledge of the mechanistic and functional effects of frequently mutated splicing factors in normal hematopoiesis and the effects of their mutations in hematologic malignancies. Moreover, we discuss the development of potential therapeutic opportunities based on these mutations.<\/jats:p>","DOI":"10.1093\/jleuko\/qiac015","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T09:56:07Z","timestamp":1673862967000},"page":"149-163","source":"Crossref","is-referenced-by-count":4,"title":["RNA splicing factors in normal hematopoiesis and hematologic malignancies: novel therapeutic targets and strategies"],"prefix":"10.1093","volume":"113","author":[{"given":"Zhenzhen","family":"Li","sequence":"first","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University , No. 127 Youyi West Road, Beilin District, Xi\u2019an, Shaanxi 710072 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongzheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mini-invasive Neurosurgery and Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University , No. 161 Xiwu Road, Xincheng District, Xi'an, Shaanxi 710003 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University , No. 127 Youyi West Road, Beilin District, Xi\u2019an, Shaanxi 710072 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyao","family":"Kong","sequence":"additional","affiliation":[{"name":"National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University , No. 157 Xiwu Road, Xincheng District, Xi'an, Shaanxi 710004 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"issue":"4","key":"2023020116345747600_qiac015-B1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2008.01.025","article-title":"Hematopoiesis: an evolving paradigm for stem cell biology","volume":"132","author":"Orkin","year":"2008","journal-title":"Cell"},{"issue":"6204","key":"2023020116345747600_qiac015-B2","doi-asserted-by":"crossref","DOI":"10.1126\/science.1251033","article-title":"Transcriptional diversity during lineage commitment of human blood progenitors","volume":"345","author":"Chen","year":"2014","journal-title":"Science"},{"issue":"2","key":"2023020116345747600_qiac015-B3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.tig.2020.09.015","article-title":"Epigenetic regulators as the gatekeepers of hematopoiesis","volume":"37","author":"Rodrigues","year":"2020","journal-title":"Trends 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