Abstract：
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Marchesini M,Ogoti Y,Fiorini E,Aktas Samur A,Nezi L,D'Anca M,Storti P,Samur MK,Ganan-Gomez I,Fulciniti MT,Mistry N,Jiang S,Bao N,Marchica V,Neri A,Bueso-Ramos C,Wu CJ,Zhang L,Liang H,Peng X,Giuliani N,Draetta Gdoi
10.1016/j.ccell.2017.05.011subject
Has Abstractpub_date
2017-07-10 00:00:00pages
88-100.e6issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(17)30207-6journal_volume
32pub_type
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