白血病中氧化还原稳态调控机制及靶向治疗策略的研究进展OA

The dynamic equilibrium between oxidative stress and antioxidant systems serves as a pivotal regu-latory mechanism in leukemogenesis,disease progression,and therapeutic responses.At low concentrations,reactive oxy-gen species(ROS)promote proliferation and immune evasion of leukemia cell through activating signaling pathways such as phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)and nuclear factor-κB(NF-κB).Different leukemia subtypes have unique redox characteristics with significant differences in ROS levels and antioxidant system activity.Leu-kemia cells have evolved robust antioxidant defense systems through the nuclear factor E2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)pathway,glutathione metabolic network,and metabolic reprogramming,thus en-abling them to maintain aberrant redox homeostasis and develop drug-resistance.In recent years,therapeutic strategies tar-geting redox homeostasis have demonstrated significant potential,and combination therapy strategies have shown synergis-tic effects.However,their clinical translation is still limited by leukemia heterogeneity,insufficient dynamic monitoring technologies,and off-target toxicity.This review has systematically summarized the regulatory mechanism of oxidative stress and antioxidant systems in leukemia and explores their potential clinical applications.