Ferroptosis: a novel therapeutic warrior in the battle against leukemia.

Abstract

Ferroptosis is a newly discovered form of iron-dependent programmed cell death, characterized by the accumulation of lethal lipid peroxidation (LPO) driven by iron overload and dysregulated intracellular redox homeostasis. Leukemia, a heterogeneous group of malignant blood system tumors, typically manifests with increased oxidative stress and iron overload. A growing body of studies have revealed intimate interactions between ferroptosis and leukemia. Induction of ferroptosis has been demonstrated to mitigate the development and progression of leukemia, thus providing novel insights into potential therapeutic strategies for leukemia. In this review, we examine the characteristics and biological processes of ferroptosis, highlighting the action mechanisms of key ferroptosis-related regulators, including iron, glutathione (GSH), glutathione peroxidase 4 (GPX4), system X_c^-, lipid reactive oxygen species (ROS), p53, and mitochondria, in contributing to leukemia. This review also underscores the significant therapeutic potential of targeting ferroptosis in leukemia therapy using regulators such as system X_c^- inhibitors, GSH/GPX4 inhibitors, lipid ROS inducers, and natural compounds. Finally, we identify key unresolved questions and challenges that warrant further investigation in future translational studies.