Haojie Dong, Xin He, Lei Zhang, Wei Chen, Yi-Chun Lin, Song-Bai Liu, Huafeng Wang, Le Xuan Truong Nguyen, Min Li, Yinghui Zhu, Dandan Zhao, Lucy Ghoda, Jonathan Serody, Benjamin Vincent, Leo Luznik, Ivana Gojo, Joshua Zeidner, Rui Su, Jianjun Chen, Ritin Sharma, Patrick Pirrotte, Xiwei Wu, Weidong Hu, Weidong Han, Binghui Shen, Ya-Huei Kuo, Jie Jin, Amandeep Salhotra, Jeffrey Wang, Guido Marcucci, Yun Lyna Luo, Ling Li
Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival...
February 27, 2024: Nature Cancer