Journal
SCIENCE ADVANCES
Volume 7, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd6280
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Funding
- National Basic Research Program of China [2019YFA0801800, 2018YFA0107000, 2019YFA0904800]
- 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 Commission [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
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A recent study has shown that B-ALL cells with low SoNar ratio preferentially use oxidative phosphorylation and are more resistant to treatment, suggesting a potential connection between metabolism and B-ALL cell fates.
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.
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