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MDS‐associated SF3B1 mutations enhance proinflammatory gene expression in patient blast cells
Author(s) -
Pollyea Daniel A.,
Kim Hyun Min,
Stevens Brett M.,
Lee Frank FangYao,
Harris Chelsea,
Hedin Brenna R.,
Knapp Jennifer R.,
O'Connor Brian P.,
Jordan Craig T.,
Pietras Eric M.,
Tan Aik Choon,
Alper Scott
Publication year - 2021
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.6ab0520-318rr
Subject(s) - biology , proinflammatory cytokine , gene , genetics , mutation , gene expression , immunology , inflammation
Two factors known to contribute to the development of myelodysplastic syndrome (MDS) and other blood cancers are (i) somatically acquired mutations in components of the spliceosome and (ii) increased inflammation. Spliceosome genes, including SF3B1 , are mutated at high frequency in MDS and other blood cancers; these mutations are thought to be neomorphic or gain‐of‐function mutations that drive disease pathogenesis. Likewise, increased inflammation is thought to contribute to MDS pathogenesis; inflammatory cytokines are strongly elevated in these patients, with higher levels correlating with worsened patient outcome. In the current study, we used RNAseq to analyze pre‐mRNA splicing and gene expression changes present in blast cells isolated from MDS patients with or without SF3B1 mutations. We determined that SF3B1 mutations lead to enhanced proinflammatory gene expression in these cells. Thus, these studies suggest that SF3B1 mutations could contribute to MDS pathogenesis by enhancing the proinflammatory milieu in these patients.