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| 基于生物信息学探究Toll 样受体7 在急性髓系白血病相关血小板减
少中的潜在免疫关联 |
| 王超群1,缴中相2,3,赵颖1,董顺利1,张先明1,朱增燕1 |
| (1. 苏州大学附属儿童医院,江苏苏州 215025;2. 中国医学科学
院血液病医院(中国医学科学院血液学研究所),血液与健康全国重点实验室,国家血液系统疾病临床医学研究中心,细胞生态
海河实验室,天津 300020;3. 天津医学健康研究院,天津 301600) |
|
| 摘要: |
| 目的:基于生物信息学方法筛选急性髓系白血病(AML)相关血小板减少中的关键基因,并探讨Toll 样受体7(TLR7) 在
AML 免疫微环境中的潜在作用。方法:基于GSE112942 中MLL-AF9 AML 小鼠巨核细胞数据筛选差异表达基因(DEG),进行基
因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析及蛋白质-蛋白质相互作用(PPI) 网络分析。比较人和小鼠TLR7
蛋白序列及关键结构域保守性,并结合TCGA、TARGET、GTEx 数据库及Sangerbox 等平台分析TLR7 在人AML 中的表达、临床
相关性及免疫浸润特征。结果:共获得605 个DEG,其中上调98 个、下调507 个,主要富集于免疫应答、炎症反应、细胞因子-细
胞因子受体相互作用及Toll 样受体信号通路。PPI 网络筛选获得TLR7 等核心基因。人和小鼠TLR7 蛋白全长序列及TIR 结构
域具有较高保守性。人源数据库分析显示,TLR7 在AML 中显著高表达,在M4、M5、M6 及M7 亚型中表达相对较高;TLR7 高表
达与较差总体生存相关,并与CD8+ T 细胞及巨噬细胞浸润水平呈正相关。结论:TLR7 可能与AML 免疫炎症微环境及巨核细
胞谱系异常存在潜在联系,可作为后续机制研究的候选分子。但目前缺乏TLR7 表达与患者血小板计数等临床表型的直接关联
证据,其在AML 相关血小板减少中的作用仍需进一步验证。 |
| 关键词: 急性髓系白血病 Toll 样受体7 血小板减少 免疫浸润 生物信息学 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2026.11.004 |
|
| 基金项目:基金项目:国家自然科学基金青年科学基金项目,编号82404691;苏州市应用基础研究(医疗卫生)科技创新重点项目,编号SYW2024005;
姑苏卫生人才计划人才科研项目,编号GSWS2023007;苏州市科技发展计划(基础研究-医学应用基础研究)项目,编号SKY2023182。 |
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| Potential Immune Association of Toll-Like Receptor 7 in Acute Myeloid Leukemia-Associated ThrombocytopeniaBased on Bioinformatics Analysis |
| Wang Chaoqun1, Jiao Zhongxiang2,3, Zhao Ying1, Dong Shunli1, Zhang Xianming1, Zhu Zengyan |
| (1. Children’s
Hospital of Soochow University, Jiangsu Suzhou 215025, China; 2. State Key Laboratory of Blood Science and Health, National Clinical
Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese
Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; 3. Tianjin Institutes of Health Science, Tianjin
301600, China) |
| Abstract: |
| Objective: To identify candidate genes associated with megakaryocytic abnormalities in acute myeloid leukemia (AML)
based on bioinformatics approaches and to explore the potential role of Toll-like receptor 7 (TLR7) in AML immune microenvironment.
Methods: Differentially expressed genes (DEG) were identified from megakaryocytes derived from an MLL-AF9 AML mouse model in
the GSE112942 dataset, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein
interaction (PPI) network analysis. Cross-species conservation of human and mouse TLR7 protein sequences and key functional domains
was evaluated. TCGA, TARGET, and GTEx datasets and the Sangerbox platform were further used to assess TLR7 expression, clinical
relevance, and immune infiltration in human AML. Results: A total of 605 DEG were identified, including 98 upregulated and 507
downregulated genes, which were mainly enriched in immune response, inflammatory response, cytokine-cytokine receptor interaction,
and Toll-like receptor signaling pathways. PPI network analysis identified TLR7 as a hub gene. Human and mouse TLR7 showed high
conservation in the full-length protein sequence and TIR domain. In human AML datasets, TLR7 was significantly overexpressed and
showed relatively high expression in FAB subtypes M4, M5, M6, and M7. High TLR7 expression was associated with poorer overall
survival and positively correlated with CD8+ T-cell and macrophage infiltration. Conclusion: TLR7 may be associated with the immuneinflammatory
microenvironment and megakaryocytic abnormalities in AML and may represent a candidate molecule for further mechanistic
investigation. However, direct clinical evidence linking TLR7 expression to platelet counts or thrombocytopenic phenotypes is currently
lacking, and its role in AML-associated thrombocytopenia requires further validation. |
| Key words: acute myeloid leukemia Toll-like receptor 7 thrombocytopenia immune infiltration bioinformatics |
