急性髓系白血病（AML）是一种常见的急性白血病，在肿瘤变异和克隆增殖引起的基因变异的影响下发展。铜死亡（cuproptosis）是一种新型的调控性细胞死亡方式。本研究旨在探讨与铜死亡相关的基因（CRGs）在AML中的作用。首先通过差异分析获得AML样本和正常样本间的差异表达基因（DEGs），然后将其与通过加权基因共表达网络分析（WGCNA）获得的与铜死亡分数相关的基因（CSRGs）相交，得到与铜死亡分数相关的差异表达基因（CS-DEGs）。随后，通过Cox分析和最小绝对收缩和选择算子（LASSO）分析构建了一个风险模型。最后，进行了免疫浸润分析，并通过单样本基因集富集分析（ssGSEA）探索了模型基因的功能和通路。通过将11,160个DEGs和132个CSRGs重叠，得到了32个CS-DEGs。这32个CS-DEGs主要富集于细胞质微管组织、RNA甲基化、mTOR信号通路和Notch信号通路。最终筛选出两个模型基因PACS2和NDUFV1来构建风险模型。此外，PACS2和NDUFV1与活化的B细胞、CD56dim自然杀伤（NK）细胞呈显著正相关，与效应记忆CD4 T细胞和活化的CD4 T细胞呈负相关。PACS2基因显著富集于肌醇磷酸盐代谢、组蛋白修饰等。NDUFV1主要富集于ncRNA代谢过程、2-羰基酸代谢等。构建了由PACS2和NDUFV1组成的与铜死亡相关的风险模型，为AML的诊断和治疗提供了新的方向。2023年《转化癌症研究》。版权所有。

Acute myeloid leukemia (AML), a common form of acute leukemia, is due to tumor changes and clonal proliferation caused by genetic variants. Cuproptosis is a novel form of regulated cell death. This study aimed to explore the role of cuproptosis-related genes (CRGs) in AML.Initially, differentially expressed genes (DEGs) between AML samples and normal samples were obtained by differential analysis, which were further intersected with the cuproptosis score-related genes (CSRGs) acquired by weighted gene co-expression network analysis (WGCNA) to obtain cuproptosis score-related differentially expressed genes (CS-DEGs). Then, a risk model was constructed by Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, immune infiltration analysis was performed and the functions and pathways of model genes were explored by single sample gene set enrichment analysis (ssGSEA).Thirty-two CS-DEGs were obtained by overlapping 11,160 DEGs and 132 CSRGs. These 32 CS-DEGs were mainly enriched to cytoplasmic microtubule organization, RNA methylation, mTOR signaling pathway, and notch signaling pathway. Two model genes, PACS2 and NDUFV1, were finally screened for the construction of the risk model. In addition, PACS2 and NDUFV1 were significantly positively correlated with activated B cells, CD56dim natural killer (NK) cells, and negatively correlated with effector memory CD4 T cells and activated CD4 T cells. PACS2 gene was significantly enriched to inositol phosphate metabolism, histone modification, etc. NDUFV1 was mainly enriched to ncRNA metabolic process, 2-oxocarboxylic acid metabolism, and other pathways.A cuproptosis-related risk model consisting of PACS2 and NDUFV1 was built, which provided a new direction for the diagnosis and treatment of AML.2023 Translational Cancer Research. All rights reserved.