Scientific publications
ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma. Scientific Publication
Matteo Marchesini 1, Yamini Ogoti 1, Elena Fiorini 1, Anil Aktas Samur 2, Luigi Nezi 3, Marianna D'Anca 1, Paola Storti 4, Mehmet Kemal Samur 2, Irene Ganan-Gomez 1, Maria Teresa Fulciniti 5, Nipun Mistry 6, Shan Jiang 3, Naran Bao 1, Valentina Marchica 4, Antonino Neri 7, Carlos Bueso-Ramos 8, Chang-Jiun Wu 3, Li Zhang 6, Han Liang 6, Xinxin Peng 6, Nicola Giuliani 4, Giulio Draetta 3, Karen Clise-Dwyer 9, Hagop Kantarjian 1, Nikhil Munshi 5, Robert Orlowski 10, Guillermo Garcia-Manero 1, Ronald A DePinho 11, Simona Colla 12
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.
CITATION Cancer Cell. 2017 Jul 10;32(1):88-100.e6. doi: 10.1016/j.ccell.2017.05.011. Epub 2017 Jun 29.
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