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正常和白血病干细胞中的代谢调控。

Metabolic regulation in normal and leukemic stem cells.

机构信息

Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Key Laboratory of Stem Cells and Tissue Engineering (Ministry of Education), Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.

Key Laboratory of Stem Cells and Tissue Engineering (Ministry of Education), Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.

出版信息

Trends Pharmacol Sci. 2024 Oct;45(10):919-930. doi: 10.1016/j.tips.2024.08.004. Epub 2024 Sep 20.

Abstract

Hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs) are crucial for ensuring hematopoietic homeostasis and driving leukemia progression, respectively. Recent research has revealed that metabolic adaptations significantly regulate the function and survival of these stem cells. In this review, we provide an overview of how metabolic pathways regulate oxidative and proteostatic stresses in HSCs during homeostasis and aging. Furthermore, we highlight targetable metabolic pathways and explore their interactions with epigenetics and the microenvironment in addressing the chemoresistance and immune evasion capacities of LSCs. The metabolic differences between HSCs and LSCs have profound implications for therapeutic strategies.

摘要

造血干细胞(HSCs)和白血病干细胞(LSCs)分别是维持造血稳态和驱动白血病进展的关键。最近的研究揭示了代谢适应对这些干细胞的功能和存活有重要的调节作用。在这篇综述中,我们概述了代谢途径如何在稳态和衰老过程中调节 HSCs 的氧化应激和蛋白质稳态。此外,我们强调了可靶向的代谢途径,并探讨了它们与表观遗传学和微环境的相互作用,以解决 LSCs 的化疗耐药性和免疫逃逸能力。HSCs 和 LSCs 之间的代谢差异对治疗策略有深远的影响。

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