Journal
CANCER CELL
Volume 32, Issue 1, Pages 88-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2017.05.011
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- AIRC [IG201415531]
- NIH [P30 CA16672, P30 CA016672]
- Cancer Center Support Grant [CA016672]
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Amplification of 1q21 occurs in approximately 30% of denovo 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.
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