[Metabolic reprogramming and the related therapeutic strategies for leukemia stem cells]

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.