铁死亡在白血病耐药中的研究进展

Research progress on roles of ferroptosis in chemotherapy resistance in leukemia

白血病的化疗耐药是临床亟待解决的治疗难题。铁死亡是铁依赖性的磷脂过氧化作用驱动的一种独特的细胞死亡方式。由于白血病的特征是氧化应激增加和铁超负荷,因此可以推测白血病细胞容易受到铁死亡的影响,这表明铁死亡具有治疗潜力。近年来,铁死亡已被广泛研究并应用于各类白血病的治疗中。目前已有多项研究表明铁死亡的调控途径与白血病耐药机制之间存在关联,通过不同途径诱导铁死亡可有效降低各类白血病细胞对化疗药物的耐药性,进而提高临床疗效。本文总结了铁死亡的调控机制,详细分析了铁死亡相关氧化应激通路及铁代谢途径与白血病耐药机制之间的关联,并梳理了铁死亡在各类白血病治疗耐药中的实验研究与临床应用,旨在为研究铁死亡与耐药性白血病的治疗提供新的思路和方向。

Chemotherapy resistance in leukemia is an urgent clinical therapeutic challenge.Ferroptosis is a unique mode of cell death driven by iron⁃dependent phospholipid peroxidation.Leukemia is characterized by increased oxidative stress and iron overload,suggesting that leukemia cells might be susceptible to ferroptosis and indicating a possible therapeutic approach.Ferroptosis has been extensively studied in recent years and used in the treatment of various types of leukemia.Several studies have demonstrated an association between the regulatory pathways of ferroptosis and the mechanisms of leukemia drug resistance.The induction of ferroptosis through different pathways can effectively reduce the resistance of various types of leukemia cells to chemotherapeutic drugs,and thus improve their clinical efficacy.In this article,we review the regulatory mechanisms of ferroptosis and analyze the association between oxidative stress and iron metabolism pathways of ferroptosis and the mechanism of leukemia drug resistance.We also summarize the experimental studies and clinical applications of ferroptosis for the treatment of various types of drug⁃resistant leukemias,with the aim of providing new ideas and directions for the study of ferroptosis and a new strategy to reverse chemotherapy resistance in patients with leukemia in the future.