Abstract：
Acute myeloid leukemia (AML) is a notably lethal disease, characterized by malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study seeks to unveil potential therapeutic targets for AML, using a combined approach of microarray analysis and Mendelian randomization (MR). We collected data samples from the Gene Expression Omnibus (GEO) database and extracted pQTL data from genome-wide association studies (GWAS) to identify overlapping genes between the DEGs and GWAS data. Gene enrichment and pathway annotation analyses were performed on these genes. Furthermore, we validated gene expression levels and assessed their clinical relevance. By taking the intersection of these gene sets, we obtained a list of co-expressed genes, including four upregulated genes (REC8, TPM2, ZMIZ1, CD82) and two downregulated genes (IFNAR1, TMCO3). MR analysis demonstrated that genetically predicted protein levels of CD82, REC8, ZMIZ1, and TPM2 were significantly associated with increased odds of AML, while IFNAR1 and TMCO3 showed a protective effect. Gene ontology and KEGG pathway analyses revealed significant enrichment in functions related to female gamete generation, meiosis, p53 signaling pathway, and cardiac muscle contraction. Differences in immune cell profiles were observed between AML survivors and those with poor prognosis, including lower levels of neutrophils and higher levels of follicular helper T cells in the latter group. This study identifies a causal relationship between gene expression and AML and highlights the potential role of REC8 in leukemogenesis, possibly through its impact on gametocyte meiotic abnormalities. The findings provide new insights into the prevention and treatment of leukemia.
摘要：
急性髓细胞性白血病（AML）是一种特别致命的疾病，以骨髓中造血干细胞的恶性克隆增殖为特征。这项研究旨在揭示AML的潜在治疗靶点。使用微阵列分析和孟德尔随机化（MR）的组合方法。我们从基因表达综合（GEO）数据库中收集了数据样本，并从全基因组关联研究（GWAS）中提取了pQTL数据，以鉴定DEGs和GWAS数据之间的重叠基因。对这些基因进行基因富集和途径注释分析。此外，我们验证了基因表达水平并评估了其临床相关性.通过获取这些基因集的交集，我们获得了共表达基因的列表，包括四个上调基因(REC8、TPM2、ZMIZ1、CD82)和两个下调基因(IFNAR1、TMCO3)。MR分析表明，基因预测的CD82，REC8，ZMIZ1和TPM2的蛋白质水平与AML的几率增加显着相关。而IFNAR1和TMCO3显示出保护作用。基因本体论和KEGG通路分析揭示了与雌性配子生成相关的功能的显着富集，减数分裂,p53信号通路,和心肌收缩。在AML幸存者和预后不良的患者之间观察到免疫细胞谱的差异。包括后一组中性粒细胞水平较低和滤泡辅助性T细胞水平较高。这项研究确定了基因表达与AML之间的因果关系，并强调了REC8在白血病发生中的潜在作用。可能是通过其对配子细胞减数分裂异常的影响。这些发现为白血病的预防和治疗提供了新的见解。
