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白血病干细胞代谢重塑及其干预策略

吴思淼¹, 印容², 张好建^1,*

¹武汉大学医学研究院，武汉 430071；²武汉大学中南医院血液科，武汉 430071

摘要

代谢重塑是白血病干细胞(leukemia stem cell, LSC)生物学特征的核心之一，也是实现选择性干预的关键窗口。不同于依赖糖酵解维持低活性氧水平的静息态造血干细胞(hematopoietic stem cell, HSC)，LSC在恶性转化过程中获得显著的代谢可塑性，能够同时利用糖酵解和氧化磷酸化(oxidative phosphorylation, OXPHOS)满足其生物合成需求并建立治疗耐药性。HSC和LSC这种差异，根植于两者在能量代谢途径、线粒体功能调控、代谢-表观遗传交叉网络等方面存在的深刻调控分歧。本文系统总结HSC与LSC代谢调控的分子基础，讨论LSC代谢重编程的调控机制，并探讨靶向LSC特异性代谢程序的精准治疗策略，为克服白血病治疗抵抗提供新思路。

关键词： 白血病干细胞; 造血干细胞; 代谢重塑; 表观调控

Metabolic reprogramming and the related therapeutic strategies for leukemia stem cells

WU Si-Miao¹, YIN Rong², ZHANG Hao-Jian^1,*

¹Medical Research Institute, Wuhan University, Wuhan 430071, China；²Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China

Abstract

Metabolic reprogramming lies at the core of the malignant features of acute myeloid leukemia stem cells (LSCs), and represents a critical window for selective targeting. Unlike quiescent hematopoietic stem cells (HSCs) that mainly rely on glycolysis to maintain low levels of reactive oxygen species, LSCs acquire remarkable metabolic plasticity during malignant transformation, enabling them to simultaneously utilize glycolysis and oxidative phosphorylation (OXPHOS) to meet biosynthetic demands and establish therapeutic resistance. These divergences between LSCs and HSCs are rooted in profound regulatory differences in terms of energy metabolism pathways, mitochondrial functional regulation and metabolic-epigenetic crosstalk networks. This review comprehensively summarizes the molecular basis of metabolic regulation in HSCs and LSCs, discusses the regulatory mechanisms of metabolic reprogramming in LSCs, and explores precise therapeutic strategies targeting the specific metabolic programs of LSCs, thereby providing new insights for overcoming therapeutic resistance in leukemia.

Key words: leukemia stem cell; hematopoietic stem cell; metabolic reprogramming; epigenetic regulation

收稿日期：　　录用日期：

通讯作者：张好建　　E-mail:

DOI: 10.13294/j.aps.2026.0082

引用本文：

吴思淼, 印容, 张好建. 白血病干细胞代谢重塑及其干预策略[J]. 生理学报 2026; 78 (4): 825-837.

WU Si-Miao, YIN Rong, ZHANG Hao-Jian. Metabolic reprogramming and the related therapeutic strategies for leukemia stem cells. Acta Physiol Sin 2026; 78 (4): 825-837 (in Chinese with English abstract).