大量研究表明，急性髓系白血病（AML）是全球死亡率较高的恶性肿瘤之一。免疫原性细胞死亡（ICD）是细胞死亡的一种形式，其特殊之处在于它会触发人体的免疫反应，特别是适应性免疫反应。最近的证据证实，假基因虽然缺乏编码蛋白的功能，但与多种人类肿瘤的发生和进展有关。然而，ICD 相关基因在 AML 中的作用在很大程度上仍未确定。TCGA-AML 和 GSE71014 队列被挑选出来，我们通过使用 R 项目中的 sva 包消除批次效应，将它们组合成一个合并数据集。对 AML 中的 ICD 基因进行共识聚类分析来定义亚组。基于 15 个预后相关假基因的表达，我们开发了一个预后模型，并将 AML 样本分为低风险组和高风险组。 AML 分为两个亚组（C1 和 C2 簇）。大多数 ICD 相关基因在 C2 簇中显着上调。单样本基因集富集分析（ssGSEA）显示，C2簇的免疫细胞浸润和免疫检查点基因表达非常高，表明C2群体对免疫检查点阻断（ICB）治疗反应良好，并且具有更好的生存率。 C1组对化疗敏感，包括阿糖胞苷、米斯托林和阿霉素。另一方面，15 个 ICD 相关假基因被鉴定与 AML 预后相关。受试者工作曲线（ROC）分析和列线图表明我们的预后模型在预测生存方面具有很高的准确性。然而，高风险组对 ICB 治疗和化疗（如甲氨蝶呤、阿糖胞苷和阿西替尼）敏感，而低风险组则受益于 5-氟尿嘧啶、他拉佐帕尼和纳维托克治疗。 总之，我们根据 33 定义了两个亚组ICD 相关基因和这种分类在评估免疫治疗和化疗获益方面发挥了决定性作用。值得注意的是，创建了由关键的 ICD 相关假基因识别的预后特征。假基因预后特征在预测预后和治疗效果（包括针对 AML 的免疫治疗和化疗）方面具有强大的性能。我们的研究指出了 ICD 对癌症预后和治疗方法选择的新意义。版权所有 © 2024 Wen、Lv、Ma、Deng、Xie 和 Yuan。

Numerous studies have demonstrated acute myeloid leukemia (AML) is one of the malignancies with high mortality worldwide. Immunogenic cell death (ICD) is a form of cell death that is specialised in that it triggers the body's immune response, particularly the adaptive immune response. Recent evidence has confirmed that pseudogenes are implicated in multiple human tumorigenesis and progression although lacking the function of coding protein. However, the roles of ICD-associated genes in AML remain largely unascertained.TCGA-AML and GSE71014 cohorts were picked out and we combined them into a merged dataset by removing the batch effect using the sva package in the R project. A consensus clustering analysis of the ICD genes in AML was performed to define subgroups. Based on the expression of 15 prognostic-related pseudogenes, we developed a prognostic model and categorized AML samples into low and high-risk groups.AML was differentiated into two subgroups (C1 and C2 clusters). Most ICD-related genes were significantly up-regulated in the C2 cluster. The single sample gene set enrichment analysis (ssGSEA) revealed that the immune cell infiltration and immune checkpoint gene expression of the C2 cluster was strongly high, suggesting that the C2 population responded well to immune checkpoint blockade (ICB) therapy and had better survival. The C1 group was sensitive to chemotherapy, including Cytarabine, Midostaurin, and Doxorubicin. On the other hand, 15 ICD-related pseudogenes were identified to be associated with AML prognosis. The receiver operator curve (ROC) analysis and nomogram manifested that our prognostic model had high accuracy in predicting survival. However, the high-risk group was sensitive to ICB therapy and chemotherapy such as Methotrexate, Cytarabine, and Axitinib while the low-risk group benefited from 5-Fluorouracil, Talazoparib, and Navitoclax therapy.In summary, we defined two subgroups relying on 33 ICD-related genes and this classification exerted a decisive role in assessing immunotherapy and chemotherapy benefit. Significantly, a prognostic signature identified by critical ICD-related pseudogene was created. The pseudogene prognostic signature had a powerful performance in predicting prognosis and therapeutic efficacy, including immunotherapy and chemotherapy to AML. Our research points out novel implications of ICD in cancer prognosis and treatment approach choice.Copyright © 2024 Wen, Lv, Ma, Deng, Xie and Yuan.