中性粒细胞胞外陷阱（NET）可归因于癌细胞的转移、发生和免疫逃避。我们研究了 NET 相关基因在儿童急性淋巴细胞白血病 (cALL) 患者中的预后价值。对从公共数据库收集的样本进行了差异基因表达分析。我们根据 NET 相关基因的表达水平对它们进行分组，评估了免疫细胞类型与 cALL 预后不良的风险评分之间的相关性，并评估了 cALL 所用药物的敏感性。我们进一步划分组，整合生存数据。随后，利用多变量 Cox 算法、最小绝对收缩和选择算子 (LASSO) 以及单变量等方法创建预测预后的风险模型。在细胞系和动物中进行实验来探索模型选择的基因 TRIM8 的功能。为了验证 TRIM8 在白血病发展中的作用，在患有 T-ALL 和 B-ALL 的小鼠中采用了慢病毒介导的 TRIM8 过表达或敲低。Kaplan-Meier (KM) 分析强调了在不同组中鉴定的差异表达基因的重要性通过基因参与 NET，富集分析显示了其机制。相关性分析显示与 B 细胞、NK 细胞、肥大细胞、T 细胞、浆细胞、树突状细胞和单核细胞显着相关。全反式维A酸(ATRA)、阿西替尼、阿霉素、甲氨蝶呤、索拉非尼和长春花碱等药物的IC50值升高，而达沙替尼的IC50值较低。 总共选择了13个NET相关基因来构建风险模型。在训练、测试和合并队列中，KM 分析表明，与高风险 cALL 患者相比，低风险 cALL 患者的生存率显着提高 (p < 0.001)。曲线下面积 (AUC) 表明预测性能很强。 Jurkat 和 SUP-B15 的实验表明，TRIM8 敲低可降低白血病细胞系的增殖。进一步的实验表明，敲除 TRIM8 的白血病细胞小鼠的预后更为良好。当 TRIM8 被敲低时，细胞系和动物的结果显示出更好的预后结果。我们在预后模型中发现了一个新颖之处，可以帮助开发针对 cALL 患者的个性化治疗。此外，研究还表明 TRIM8 的表达是白血病细胞增殖的一个促进因素，并使 cALL 的预后恶化。版权所有 © 2024 Tin、Xiao、Sun、Zhao、Xie、Zheng、Wang、Liu 和 Yu。

Neutrophil extracellular traps (NETs) can be attributed to the metastasis, occurrence, and immune evasion of cancer cells. We investigated the prognostic value of NET-related genes in childhood acute lymphoblastic leukemia (cALL) patients.Differential gene expression analysis was conducted on samples collected from public databases. Grouping them based on the expression level of NET-related genes, we assessed the correlation between immune cell types and the risk score for having a poor prognosis of cALL, with an evaluation of the sensitivity of drugs used in cALL. We further divided the groups, integrating survival data. Subsequently, methods including multivariable Cox algorithms, least absolute shrinkage and selection operator (LASSO), and univariable were utilized to create a risk model predicting prognosis. Experiments in cell lines and animals were performed to explore the functions of TRIM8, a gene selected by the model. To validate the role of TRIM8 in leukemia development, lentivirus-mediated overexpression or knockdown of TRIM8 was employed in mice with T-ALL and B-ALL.Kaplan-Meier (KM) analysis underscored the importance of differentially expressed genes identified in the groups divided by genes participated in NETs, with enrichment analysis showing the mechanism. Correlation analysis revealed significant associations with B cells, NK cells, mast cells, T cells, plasma cells, dendritic cells, and monocytes. The IC50 values of drugs such as all-trans-retinoic acid (ATRA), axitinib, doxorubicin, methotrexate, sorafenib, and vinblastine were increased, while dasatinib exhibited a lower IC50. A total of 13 NET-related genes were selected in constructing the risk model. In the training, testing, and merged cohorts, KM analysis demonstrated significantly improved survival for low-risk cALL patients compared to high-risk cALL patients (p < 0.001). The area under the curve (AUC) indicated strong predictive performance. Experiments in Jurkat and SUP-B15 revealed that TRIM8 knockdown decreased the proliferation of leukemia cell lines. Further experiments demonstrated a more favorable prognosis in mice with TRIM8-knockdown leukemia cells. Results of cell lines and animals showed better outcomes in prognosis when TRIM8 was knocked down.We identified a novelty in a prognostic model that could aid in the development of personalized treatments for cALL patients. Furthermore, it revealed that the expression of TRIM8 is a contributing factor to the proliferation of leukemia cells and worsens the prognosis of cALL.Copyright © 2024 Tin, Xiao, Sun, Zhao, Xie, Zheng, Wang, Liu and Yu.