孟德尔随机化分析揭示了免疫细胞与白血病之间的因果关系。

Mendelian randomization analysis reveals the causal relationship between immune cells and leukemia.

作者信息

Lin Yaobin, Shi Shenghong, Song Jianyuan, Liu Shan

机构信息

Department of Radiation Oncology, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fujian Medical University Union Hospital, Fuzhou, 350000, Fujian, China.

Department of Hematology-Oncology, Fujian Children's Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, Fujian, China.

出版信息

Discov Oncol. 2025 May 20;16(1):836. doi: 10.1007/s12672-025-02735-5.

Abstract

BACKGROUND

Increasing evidence indicates certain types of immune cells are linked to leukemia, but whether this link is causal has remained unclear.

METHODS

A two-sample Mendelian randomization (MR) analysis was conducted to examine the causal relationship (CR) among 731 immune cell traits and leukemia. The inverse variance weighted (IVW) technique was applied, along with the weighted median and MR-Egger approaches, to analyze the data. The instrumental variables were validated for heterogeneity and pleiotropy using sensitivity analyses.

RESULTS

A total of 58 immune cell traits with CRs with leukemia were identified, of which 15 were considered risk factors for leukemia. The factors were distributed among acute myeloid leukemia (AML) (3 traits), acute lymphoblastic leukemia (ALL) (4 traits), chronic myeloid leukemia (CML) (3 traits), and chronic lymphocytic leukemia (CLL) (5 traits). Additionally, 43 immune traits were considered protective factors for leukemia and were distributed among ALL (15 traits), AML (9 traits), CLL (18 traits), and CML (1 trait). After FDR correction, it was found that terminally differentiated CD4 + T cell absolute count is a protective factor for CLL. Immune traits with CRs between both types of leukemia included "CD62L-plasmacytoid dendritic cell %," "plasmacytoid dendritic cell absolute count," "CD11c on granulocytes," "HLA DR + CD8 + T cell %lymphocytes," "HLA DR + CD8 + T cell %," "HLA DR + T cell %," "CD28 on CD28 + CD45RA + CD8 + T cells," "HLA DR + CD4 + T cell absolute count," and "CD45RA- CD28- CD8 + T cell absolute count."

CONCLUSIONS

The results of this investigation reveal that leukemia closely relates to specific types of immune cells. Our findings provide a scientific basis for further investigations into factors that will improve immunotherapy.

摘要

背景

越来越多的证据表明,某些类型的免疫细胞与白血病有关,但这种联系是否具有因果关系尚不清楚。

方法

进行了一项两样本孟德尔随机化(MR)分析,以研究731种免疫细胞特征与白血病之间的因果关系(CR)。应用逆方差加权(IVW)技术以及加权中位数和MR-Egger方法来分析数据。使用敏感性分析对工具变量的异质性和多效性进行了验证。

结果

共确定了58种与白血病存在因果关系的免疫细胞特征,其中15种被认为是白血病的危险因素。这些因素分布在急性髓系白血病(AML)(3种特征)、急性淋巴细胞白血病(ALL)(4种特征)、慢性髓系白血病(CML)(3种特征)和慢性淋巴细胞白血病(CLL)(5种特征)中。此外,43种免疫特征被认为是白血病的保护因素,分布在ALL(15种特征)、AML(9种特征)、CLL(18种特征)和CML(1种特征)中。经过错误发现率(FDR)校正后,发现终末分化的CD4 + T细胞绝对计数是CLL的保护因素。两种白血病之间存在因果关系的免疫特征包括“CD62L+浆细胞样树突状细胞百分比”、“浆细胞样树突状细胞绝对计数”、“粒细胞上的CD11c”、“HLA DR+CD8+T细胞占淋巴细胞的百分比”、“HLA DR+CD8+T细胞百分比”、“HLA DR+T细胞百分比”、“CD28+CD45RA+CD8+T细胞上的CD28”、“HLA DR+CD4+T细胞绝对计数”和“CD45RA-CD28-CD8+T细胞绝对计数”。

结论

本研究结果表明白血病与特定类型的免疫细胞密切相关。我们的发现为进一步研究改善免疫治疗的因素提供了科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939a/12092886/d275ffbf4163/12672_2025_2735_Fig1_HTML.jpg

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