期刊
FRONTIERS IN ONCOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.807266
关键词
acute myeloid leukaemia; metabolic plasticity; leukaemic stem cells; cancer metabolism; metabolic targeting
类别
资金
- Tour de Cure Pioneering Grant (Tour De Cure, Australia) [RSP-00122-19/20]
- National Health and Medical Research Council of Australia [APP1059804, APP1157871]
- Research Training Program Scholarship (RTP)
Targeting the metabolic characteristics of AML cells holds promise for the treatment of AML relapse. The metabolic differences between normal hematopoietic cells, AML cells, and LSCs are being studied, and drug interventions exploiting the metabolic vulnerabilities of AML cells are being explored.
Despite intensive chemotherapy regimens, up to 60% of adults with acute myeloid leukaemia (AML) will relapse and eventually succumb to their disease. Recent studies suggest that leukaemic stem cells (LSCs) drive AML relapse by residing in the bone marrow niche and adapting their metabolic profile. Metabolic adaptation and LSC plasticity are novel hallmarks of leukemogenesis that provide important biological processes required for tumour initiation, progression and therapeutic responses. These findings highlight the importance of targeting metabolic pathways in leukaemia biology which might serve as the Achilles' heel for the treatment of AML relapse. In this review, we highlight the metabolic differences between normal haematopoietic cells, bulk AML cells and LSCs. Specifically, we focus on four major metabolic pathways dysregulated in AML; (i) glycolysis; (ii) mitochondrial metabolism; (iii) amino acid metabolism; and (iv) lipid metabolism. We then outline established and emerging drug interventions that exploit metabolic dependencies of leukaemic cells in the treatment of AML. The metabolic signature of AML cells alters during different biological conditions such as chemotherapy and quiescence. Therefore, targeting the metabolic vulnerabilities of these cells might selectively eradicate them and improve the overall survival of patients with AML.
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