机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.[2]Department of Hematology, Shanghai Zhaxin Hospital, Shanghai 200434, China.[3]Center of Reproductive Medicine, Shanghai Sixth People’s Hospital, 600 Yishan Road Shanghai 200233, China.[4]Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.[5]East Hospital, Tongji University School of Medicine, Shanghai 200120, China.[6]Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences, Beijing, China.[7]The Fifth People’s Hospital of Shanghai, Fudan University, and The Shanghai Key Laboratory of Medical Epigenetics, The International Co-Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.[8]Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
How metabolic status controls the fates of different types of leukemia cells remains elusive. Using a SoNar-transgenic mouse line, we demonstrated that B cell acute lymphoblastic leukemia (B-ALL) cells had a preference in using oxidative phosphorylation. B-ALL cells with a low SoNar ratio (SoNar-low) had enhanced mitochondrial respiration capacity, mainly resided in the vascular niche, and were enriched with more functional leukemia-initiating cells than that of SoNar-high cells in a murine B-ALL model. The SoNar-low cells were more resistant to cytosine arabinoside (Ara-C) treatment. cyclic adenosine 3',5'-monophosphate response element-binding protein transactivated pyruvate dehydrogenase complex component X and cytidine deaminase to maintain the oxidative phosphorylation level and Ara-C-induced resistance. SoNar-low human primary B-ALL cells also had a preference for oxidative phosphorylation. Suppressing oxidative phosphorylation with several drugs sufficiently attenuated Ara-C-induced resistance. Our study provides a unique angle for understanding the potential connections between metabolism and B-ALL cell fates.
基金：
National Basic Research Program of ChinaNational Basic Research Program of China [2019YFA0801800, 2018YFA0107000, 2019YFA0904800]; National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [81825001, 81570093, 31971052, 81900147, 81461138037, 31722033, 32030065, 31671484, 81873438, 82000147]; innovative group of NSFC [81721004]; Shanghai Science and Technology CommissionShanghai Science & Technology CommitteeScience & Technology Commission of Shanghai Municipality (STCSM) [19XD1422100, 17ZR1415500, 20JC1412000]; National Major Scientific and Technological Special Project for "Significant new drugs development" [2018ZX09201002-005]; Research Unit of New Techniques for Live-Cell Metabolic Imaging (Chinese Academy of Medical Sciences) [2019RU01, 2019-I2M-5-013]; Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone (Stem Cell Strategic Biobank and Stem Cell Clinical Technology Transformation Platform) [ZJ2018-ZD-004]; innovative research team of high-level local universities in Shanghai
第一作者机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
共同第一作者：
通讯作者：
通讯机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.[4]Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.[6]Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences, Beijing, China.[8]Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
推荐引用方式(GB/T 7714)：
Chen Chiqi,Hao Xiaoxin,Lai Xiaoyun,et al.Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia[J].SCIENCE ADVANCES.2021,7(11):doi:10.1126/sciadv.abd6280.
APA：
Chen, Chiqi,Hao, Xiaoxin,Lai, Xiaoyun,Liu, Ligen,Zhu, Jun...&Zheng, Junke.(2021).Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia.SCIENCE ADVANCES,7,(11)
MLA：
Chen, Chiqi,et al."Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia".SCIENCE ADVANCES 7..11(2021)
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