免疫细胞与急性髓系白血病的因果关联：一项孟德尔随机化研究-现代医学

免疫细胞与急性髓系白血病的因果关联：一项孟德尔随机化研究

单位：广东医科大学附属医院血液内科, 广东湛江 524002

分类号：R552;R733.71

出版年·卷·期（页码）：2025·53·第三期（371-381）

摘要：

目的：采用孟德尔随机化(MR)分析免疫细胞与急性髓系白血病(AML)的因果效应。方法：基于GWAS Catalogue数据库获取731种免疫细胞数据，FinnGen R10数据库中获取AML遗传数据，采用加权中位数估计(WME)和逆方差加权(IVW)法进行分析，通过Cochran Q检验、MR-PRESSO、MR-Egger和逐一排除等方法进行敏感性分析以评估其稳健性。通过反向MR分析阐明AML与免疫细胞的关系。结果： 5种免疫细胞被确定与AML的发生显著相关，在B细胞中，CD24⁺ CD27⁺ B细胞上的CD19表达水平被识别为AML的风险因素, 而幼稚-成熟B细胞占淋巴细胞的百分比则作为保护因素；在T细胞中，CD45RA^-CD4⁺ T细胞绝对计数被识别为保护因素，而静息CD4调节性T细胞占CD4调节性T细胞的百分比和静息CD4调节性T细胞占CD4⁺ T细胞的百分比则被识别为风险因素。反向MR分析显示，AML与静息CD4调节性T细胞占CD4调节性T细胞的百分比之间存在正相关。结论： MR分析揭示了5种免疫细胞与AML之间的因果关系，为发展新型免疫疗法提供了新视角。

Objective: To investigating the causal effects of immune cells and acute myeloid leukemia(AML) through Mendelian randomization analysis. Methods: 731 types of immune cells were obtained from the GWAS Catalogue database and AML genetic data were obtained from the FinnGen R10 database. Weighted median estimation(WME) and inverse variance weighting(IVW) methods were used for analysis. The robustness of the obtained results was evaluated by sensitivity analysis using Cochran Q test, MR-PRESSO, MR-Egger and leave-one-out. Results: Five types of immune cells were identified to be significantly associated with the occurrence of AML. In B cells, CD19 on CD24⁺ CD27⁺ B cell was recognized as a risk factor for AML, percentage of naive-mature B cell in lymphocyte served as a protective factor. In T cells, CD45RA^- CD4⁺ T cell absolute count was recognized as a protective factor, whereas percentage of resting CD4 regulatory T cell in CD4 regulatory T cell and the percentage of resting CD4 regulatory T cell in CD4⁺ T cell were recognized as risk factors. Reverse MR analysis revealed a positive correlation between AML and percentage of resting CD4 regulatory T cell in CD4 regulatory T cell. Conclusion: MR analysis reveals the causal relationship between five types of immune cells and AML, providing a new perspective for the development of new immunotherapies.

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