磷脂氢过氧化物谷胱甘肽过氧化物酶也称为谷胱甘肽过氧化物酶 4，是 25 种人类硒蛋白之一。它在消除有毒的脂质羟基过氧化物方面发挥着重要作用，从而抑制铁死亡并有利于细胞存活。 GPX4根据骨髓分化阶段而存在差异表达，在造血干细胞和多形核白细胞中表达较低，而在髓系祖细胞和单核细胞中表达较高水平。此外，与正常造血干细胞相比，GPX4在大多数急性髓系白血病（AML）亚型中高表达。 GPX4 高表达始终与 AML 患者的不良预后相关。然而，GPX4 在髓系谱系的发育以及髓系白血病的发生和进展中的作用仍知之甚少。鉴于其在脂质过氧化氢解毒中的重要作用及其在大多数骨髓恶性肿瘤中的过度表达，GPX4 抑制已成为一种有前景的治疗策略，可特异性触发铁死亡和根除骨髓性白血病细胞。在这篇综述中，我们描述了有关 GPX4 的作用以及更普遍的髓系铁死亡和 AML 出现中的作用的最新进展。我们还讨论了单独使用 GPX4 抑制或与其他药物联合使用作为治疗 AML 患者的创新疗法的治疗兴趣和局限性。© 2024。作者。

Phospholipid Hydroperoxide Gluthatione Peroxidase also called Glutathione Peroxidase 4 is one of the 25 described human selenoproteins. It plays an essential role in eliminating toxic lipid hydroxy peroxides, thus inhibiting ferroptosis and favoring cell survival. GPX4 is differentially expressed according to myeloid differentiation stage, exhibiting lower expression in hematopoietic stem cells and polymorphonuclear leucocytes, while harboring higher level of expression in common myeloid progenitors and monocytes. In addition, GPX4 is highly expressed in most of acute myeloid leukemia (AML) subtypes compared to normal hematopoietic stem cells. High GPX4 expression is consistently correlated to poor prognosis in patients suffering AML. However, the role of GPX4 in the development of the myeloid lineage and in the initiation and progression of myeloid leukemia remains poorly explored. Given its essential role in the detoxification of lipid hydroperoxides, and its overexpression in most of myeloid malignancies, GPX4 inhibition has emerged as a promising therapeutic strategy to specifically trigger ferroptosis and eradicate myeloid leukemia cells. In this review, we describe the most recent advances concerning the role of GPX4 and, more generally ferroptosis in the myeloid lineage and in the emergence of AML. We also discuss the therapeutic interest and limitations of GPX4 inhibition alone or in combination with other drugs as innovative therapies to treat AML patients.© 2024. The Author(s).