铜死亡，首次登上Cell期刊：诱发铜死亡，治疗白血病

Core Viewpoint - The research identifies a novel copper-dependent cell death mechanism named Cuprotosis, which is triggered by the accumulation of copper ions and is linked to the inhibition of heme biosynthesis in acute myeloid leukemia (AML) cells, presenting a potential therapeutic target in AML treatment [2][4][12]. Group 1: Research Findings - The study published by Todd Golub's team reveals that Cuprotosis is a distinct form of cell death, different from apoptosis, necroptosis, and ferroptosis, involving the interaction of copper ions with mitochondrial proteins [2][8]. - Inhibition of heme biosynthesis leads to copper accumulation in AML cells, activating Cuprotosis and indicating that heme biosynthesis enzyme (HBE) is a promising drug target for AML [4][10]. - The research demonstrates that heme depletion triggers mitochondrial complex IV collapse, resulting in copper accumulation and subsequent Cuprotosis [10][12]. Group 2: Implications for AML Treatment - The findings suggest that targeting HBE could enhance the effectiveness of AML therapies by inducing Cuprotosis, addressing the urgent need for new treatment strategies due to common resistance and relapse in existing therapies [6][12]. - The study highlights the metabolic reprogramming in AML as a key feature, providing a basis for developing therapies that target metabolic pathways, including heme biosynthesis [6][9]. - The research indicates that the relationship between heme levels and leukemia transcription programs could be exploited for therapeutic interventions, offering new avenues for AML treatment [10][12].