| Literature DB >> 28669490 |
Matteo Marchesini1, Yamini Ogoti1, Elena Fiorini1, Anil Aktas Samur2, Luigi Nezi3, Marianna D'Anca1, Paola Storti4, Mehmet Kemal Samur2, Irene Ganan-Gomez1, Maria Teresa Fulciniti5, Nipun Mistry6, Shan Jiang3, Naran Bao1, Valentina Marchica4, Antonino Neri7, Carlos Bueso-Ramos8, Chang-Jiun Wu3, Li Zhang6, Han Liang6, Xinxin Peng6, Nicola Giuliani4, Giulio Draetta3, Karen Clise-Dwyer9, Hagop Kantarjian1, Nikhil Munshi5, Robert Orlowski10, Guillermo Garcia-Manero1, Ronald A DePinho11, Simona Colla12.
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.Entities:
Keywords: 1q21 amplification; DNA damage; DNA repair; ILF2; multiple myeloma; splicing
Mesh：
Substances：
Year: 2017 PMID： 28669490 PMCID： PMC5593798 DOI： 10.1016/j.ccell.2017.05.011
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743