Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia

Cancer Cell. 2016 Nov 14;30(5):750-763. doi: 10.1016/j.ccell.2016.10.005. Epub 2016 Nov 3.


Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.

Keywords: CLL; Notch signaling; RNA sequencing; SF3B1; alternative splicing.

MeSH terms

  • Alternative Splicing*
  • Cell Line, Tumor
  • Dishevelled Proteins / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Mutation*
  • Phosphoproteins / genetics*
  • RNA Splicing Factors / genetics*
  • Receptors, Notch / genetics
  • Signal Transduction


  • DVL2 protein, human
  • Dishevelled Proteins
  • Phosphoproteins
  • RNA Splicing Factors
  • Receptors, Notch
  • SF3B1 protein, human