急性髓系白血病（AML）是一种多样化的恶性肿瘤，其预后各不相同，对于老年患者和具有高危特征的患者尤其不利。代谢重编程已成为 AML 发展的重要因素，为预后评估和治疗干预提供了新的机会。通过将 KEGG 代谢基因列表与来自 GSE63270 的 AML 基因表达数据整合，鉴定了代谢相关差异表达基因 (mDEG)。使用 TCGA 数据，我们进行了共识聚类和生存分析，以研究 mDEG 的预后意义。使用 LASSO Cox 回归构建代谢风险模型，并通过结合临床特征的列线图进行增强。该模型通过受试者工作特征（ROC）曲线和生存统计进行验证。进行基因网络分析以确定关键的预后因素。使用CIBERSORT和ESTIMATE算法评估肿瘤免疫微环境，然后进行免疫检查点基因表达与风险评分之间的相关性分析。通过药物敏感性预测和体外实验来探讨 mDEG 对细胞增殖和化疗耐药的影响。建立并验证了 11 基因代谢预后模型。高风险患者在训练组和验证组中的总生存期均较差 (p < 0.05)。风险评分是一个独立的预后因素。高风险患者表现出免疫细胞浸润增加和对检查点抑制剂的潜在反应，但药物敏感性降低。该模型与对维奈托克等药物的敏感性相关。碳酸酐酶 13 (CA13) 被确定为与预后和阿霉素耐药性相关的关键基因。通过多柔比星治疗，敲低 CA13 可减少增殖并增加细胞死亡。开发了一种新的代谢基因特征来对 AML 风险进行分层并预测预后，作为独立的预后因素。 CA13被确定为潜在的治疗靶点。这项研究为 AML 中代谢基因的预后和治疗意义提供了新的见解。版权所有 © 2024 Ren、Wang、Li、Yin、Li 和 Wang。

Acute myeloid leukemia(AML) is a diverse malignancy with a prognosis that varies, being especially unfavorable in older patients and those with high-risk characteristics. Metabolic reprogramming has become a significant factor in AML development , presenting new opportunities for prognostic assessment and therapeutic intervention.Metabolism-related differentially expressed genes (mDEGs) were identified by integrating KEGG metabolic gene lists with AML gene expression data from GSE63270. Using TCGA data, we performed consensus clustering and survival analysis to investigate the prognostic significance of mDEGs. A metabolic risk model was constructed using LASSO Cox reg ression and enhanced by a nomogram incorporated clinical characteristics. The model was validated through receiver operating characteristic (ROC) curves and survival statistics. Gene network analysis was conducted to identify critical prognostic factors. The tumor immune microenvironment was evaluated using CIBERSORT and ESTIMATE algorithms, followed by correlation analysis between immune checkpoint gene expression and risk scores. Drug sensitivity predictions and in vitro assays were performed to explore the effects of mDEGs on cell proliferation and chemoresistance.An 11-gene metabolic prognostic model was established and validated. High-risk patients had worse overall survival in both training and validation cohorts (p < 0.05). The risk score was an independent prognostic factor. High-risk patients showed increased immune cell infiltration and potential response to checkpoint inhibitors but decreased drug sensitivity. The model correlated with sensitivity to drugs such as venetoclax. Carbonic anhydrase 13 (CA13) was identified as a key gene related to prognosis and doxorubicin resistance. Knocking down CA13 reduced proliferation and increased cell death with doxorubicin treatment.A novel metabolic gene signature was developed to stratify risk and predict prognosis in AML, serving as an independent prognostic factor. CA13 was identified as a potential therapeutic target. This study provides new insights into the prognostic and therapeutic implications of metabolic genes in AML.Copyright © 2024 Ren, Wang, Li, Yin, Li and Wang.