Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cells. 2023 Apr 11;12(8):1128. doi: 10.3390/cells12081128.
Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is largely lacking. In this review, we summarize the current understanding of ferroptosis-regulating mechanisms with respect to the metabolism of phospholipids and iron as well as major anti-oxidative pathways that protect cells from ferroptosis. We also highlight the diverse impact of p53, a master regulator of cell death and cellular metabolic processes, on the regulation of ferroptosis. Lastly, we discuss recent ferroptosis studies in leukemia and provide a future perspective for the development of promising anti-leukemia therapies implementing ferroptosis induction.
铁死亡是一种受铁依赖性脂质过氧化调控的细胞死亡方式。越来越多的证据表明，铁死亡诱导可能是一种新的抗癌模式，有可能克服癌症的治疗耐药性。参与铁死亡调控的分子机制复杂且高度依赖于背景。因此，为了实施这种独特的细胞死亡模式以靶向个别癌症，有必要全面了解其在每种肿瘤类型中的执行和保护机制。由于目前关于铁死亡调控机制的大部分证据都基于实体瘤研究，因此关于白血病的铁死亡知识在很大程度上仍然缺乏。在这篇综述中，我们总结了目前对铁死亡调控机制的理解，包括磷脂和铁代谢以及主要的抗氧化途径，这些途径可以保护细胞免受铁死亡。我们还强调了细胞死亡和细胞代谢过程的主要调节因子 p53 对铁死亡调节的多样化影响。最后，我们讨论了白血病中铁死亡的最新研究，并为开发实施铁死亡诱导的有前途的抗白血病疗法提供了未来的展望。
