Article
TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma.
Nature communications - 27 Sept 2022
Erazo Tatiana, Evans Chiara M, Zakheim Daniel, Chu Eren L, Refermat Alice Yunsi, Asgari Zahra, Yang Xuejing, Da Silva Ferreira Mariana, Mehta Sanjoy, Russo Marco Vincenzo, Knezevic Andrea, Zhang Xi-Ping, Chen Zhengming, Fennell Myles, Garippa Ralph, Seshan Venkatraman, de Stanchina Elisa, Barbash Olena, Batlevi Connie Lee, Leslie Christina S, Melnick Ari M, Younes Anas, Kharas Michael G
Abstract excerpt
To identify drivers of sensitivity and resistance to Protein Arginine Methyltransferase 5 (PRMT5) inhibition, we perform a genome-wide CRISPR/Cas9 screen. We identify TP53 and RNA-binding protein MUSASHI2 (MSI2) as the top-ranked sensitizer and driver of resistance to specific PRMT5i, GSK-591, respectively. TP53 deletion and TP53R248W mutation are biomarkers of resistance to GSK-591. PRMT5 expression correlates...
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