ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma

Cancer Cell. 2017 Jul 10;32(1):88-100.e6. doi: 10.1016/j.ccell.2017.05.011. Epub 2017 Jun 29.


Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistance to DNA-damaging agents. Mechanistically, elevated ILF2 expression exerts resistance to genotoxic agents by modulating YB-1 nuclear localization and interaction with the splicing factor U2AF65, which promotes mRNA processing and the stabilization of transcripts involved in homologous recombination in response to DNA damage. The intimate link between 1q21-amplified ILF2 and the regulation of RNA splicing of DNA repair genes may be exploited to optimize the use of DNA-damaging agents in patients with high-risk MM.

Keywords: 1q21 amplification; DNA damage; DNA repair; ILF2; multiple myeloma; splicing.

Publication types

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

MeSH terms

  • DNA Damage
  • DNA Repair
  • Homologous Recombination
  • Humans
  • Multiple Myeloma / genetics*
  • Nuclear Factor 45 Protein / genetics
  • Nuclear Factor 45 Protein / metabolism
  • Nuclear Factor 45 Protein / physiology*
  • RNA Splicing / genetics*
  • Splicing Factor U2AF / metabolism
  • Tumor Cells, Cultured
  • Y-Box-Binding Protein 1 / metabolism


  • ILF2 protein, human
  • Nuclear Factor 45 Protein
  • Splicing Factor U2AF
  • Y-Box-Binding Protein 1
  • YBX1 protein, human