biostudies-literatureDolatshad HMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Trust1092-103https://www.ebi.ac.uk/biostudies/studies/S-EPMC4430703biostudies-literatureUnknown29(5)The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenLeukemiaDisruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.PMC4430703RP-PG-0310-1004088340090532/Z/09/ZG0900747 91070Boultwood JLockstone HScifo LCazzola MCampbell PJSavage KIAttwood MPapaemmanuil ESahgal NDolatshad HFernandez-Mercado MPellagatti AVandenberghe PSmith CWPrzychodzen BOgawa SYip BHKanapin AAMalcovati LMaciejewski JPfalseDisruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogen2015-01-01T00:00:00Z2015 May2026-05-03T03:03:38.529Z2019-03-27T01:51:35ZS-EPMC44307032542826210.1038/leu.2014.331