MDS-associated SF3B1 mutations enhance proinflammatory gene expression in patient blast cells

J Leukoc Biol. 2021 Jul;110(1):197-205. doi: 10.1002/JLB.6AB0520-318RR. Epub 2020 Nov 6.


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.

Keywords: RNAseq; inflammation; pre-mRNA splicing; spliceosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / metabolism
  • Gene Expression*
  • Humans
  • Inflammation Mediators / metabolism
  • Mutation*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology
  • Phosphoproteins / genetics*
  • RNA Splicing
  • RNA Splicing Factors / genetics*
  • Spliceosomes / metabolism
  • Stem Cells / metabolism*


  • Cytokines
  • Inflammation Mediators
  • Phosphoproteins
  • RNA Splicing Factors
  • SF3B1 protein, human