Dan Huang, Changcheng Zhang, Ming Xiao, Xie Li, Weicai Chen, Yu Jiang, Yamin Yuan, Yaping Zhang, Yejun Zou, Lei Deng, Yang Wang, Yuying Sun, Wenping Dong, Zhuo Zhang, Li Xie, Zhuo Yu, Chiqi Chen, Ligen Liu, Jing Wang, Yi Yang, Jie Yang, Yuzheng Zhao, Junke Zheng
Rewiring of redox metabolism has a profound impact on tumor development, but how the cellular heterogeneity of redox balance affects leukemogenesis remains unknown. To precisely characterize the dynamic change in redox metabolism in vivo, we developed a bright genetically encoded biosensor for H2 O2 (named HyPerion) and tracked the redox state of leukemic cells in situ in a transgenic sensor mouse. A H2 O2 -low (HyPerion-low) subset of acute myeloid leukemia (AML) cells was enriched with leukemia-initiating cells, which were endowed with high colony-forming ability, potent drug resistance, endosteal rather than vascular localization, and short survival...
March 28, 2023: Proceedings of the National Academy of Sciences of the United States of America