Abstract
Acute myeloid leukaemia (AML) cells metabolise glucose by glycolysis-based re-programming. However, how glucose uptake is partitioned between leukaemia cells and other cells of the bone marrow micro-environment is unstudied. We used a positron emission tomography (PET) tracer 18F fluorodeoxyglucose ([18F]-FDG) probe and transcriptomic analyses to detect glucose uptake by diverse cells in the bone marrow micro-environment in a MLL-AF9-induced mouse model. Leukaemia cells had the greatest glucose uptake with leukaemia stem and progenitor cells having the greatest glucose uptake. We also show the effects of anti-leukaemia drugs on leukaemia cell numbers and glucose uptake. Our data suggest targeting glucose uptake as a potential therapy strategy in AML if our observations are validated in humans with AML.
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Data availability
Data are available in the text and supplement. Raw transcriptomic data have been submitted to GEO database under the accession number GSE227584. R scripts are available upon reasonable request from HZ.
Code availability
Data are available in the text and supplement. Raw transcriptomic data have been submitted to GEO database under the accession number GSE227584. R scripts are available upon reasonable request from HZ.
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Acknowledgements
Drs. Xiaoping Yi (Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China) and Xiaoxia Hu (Collaborative Innovation Centre of Haematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China) kindly reviewed the typescript. RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre.
Funding
Supported, in part, by the Talent Young Programme of Guangdong Province (2021B1515020017), National Natural Science Foundation of China (Grant No. 81970143 and No. 82270167), Municipal School Joint Programme from Guangzhou Science and Technological Project (202201020012) and the Leading Talents Programme from The First Affiliated Hospital of Jinan University to HZ.
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SQD data curation, experiment conduction, statistical and transcriptomic analysis, visualisation, preparing the typescript. JD data curation, result interpretation, investigation, preparing and editing the typescript. RPG, data interpretation, reviewing and editing the typescript. LW technical support. HEZ, FSL, KXH experimental assistance. HX technical support. HZ project design, investigation, data interpretation, reviewing and editing the typescript. All authors take responsibility for the content of the typescript and agreed to submit for publication.
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RPG is a consultant to NexImmune Inc. Nanexa Pharma Ascentage Pharm Group and Antengene Biotech LLC, Medical Director of FFF Enterprises Inc.; Partner in AZCA Inc.; Board of Directors of Russian Foundation for Cancer Research Support and Scientific Advisory Board: StemRad Ltd.
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Deng, S., Du, J., Gale, R.P. et al. Glucose partitioning in the bone marrow micro-environment in acute myeloid leukaemia. Leukemia 37, 1407–1412 (2023). https://doi.org/10.1038/s41375-023-01912-1
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DOI: https://doi.org/10.1038/s41375-023-01912-1