Jing Xu, Ailing Zhong, Shan Zhang, Mei Chen, Lanxin Zhang, Xiaohang Hang, Jianan Zheng, Baohong Wu, Xintong Deng, Xiangyu Pan, Zhongwang Wang, Lu Qi, Kaidou Shi, Shujun Li, Yiyun Wang, Manli Wang, Xuelan Chen, Qi Zhang, Pengpeng Liu, Robert Peter Gale, Chong Chen, Yu Liu, Ting Niu
KMT2C and KMT2D are the most frequently mutated epigenetic genes in human cancers. While KMT2C is identified as a tumor suppressor in acute myeloid leukemia (AML), the role of KMT2D remains unclear in this disease, though its loss promotes B cell lymphoma and various solid cancers. Here, it is reported that KMT2D is downregulated or mutated in AML and its deficiency, through shRNA knockdown or CRISPR/Cas9 editing, accelerates leukemogenesis in mice. Hematopoietic stem and progenitor cells and AML cells with Kmt2d loss have significantly enhanced ribosome biogenesis and consistently, enlarged nucleolus, increased rRNA and protein synthesis rates...
May 4, 2023: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)