急性髓系白血病（AML）是一种儿科患者中常见的白血病，治愈率低且预后差。AML免疫微环境和甲基化的调控有待探索。儿童和成年AML患者的表观遗传因子存在显著差异，并且治疗方法的效率在这两组患者之间有所不同。我们从多个数据库收集了儿童AML患者的mRNA、miRNA和DNA甲基化数据。鉴定出差异表达基因，并构建了基因-miRNA调控网络。通过整合LASSO和Cox回归建立了预后风险模型，并生成了一张示意图。基于该模型，我们研究了肿瘤浸润的免疫细胞和细胞间通信，分析了与预后因素相关的生物学功能和通路。此外，我们探讨了所有预后因素与基因模块之间的关系，并确定了这些因素对治疗方法的影响。我们开发了一个高效的预后风险模型，并确定了HOXA9、SORT1、SH3BP5、mir-224和mir-335作为生物标志物。我们在外部数据集中验证了这些发现，并观察到年龄与儿童患者风险之间的相关性。风险评分较低的AML样本具有更好的预后和更高的免疫上调生物标志物表达，而且免疫评分较低。此外，我们还检测到高风险组和低风险组样本之间在免疫细胞浸润和相互作用方面存在差异，这影响了免疫疗法的疗效。我们评估了所有预后因素，并预测了免疫疗法和药物的效果。本研究全面调查了儿童AML的甲基化标记基因在基因组和转录组水平上的作用。本研究旨在增强AML患者的风险分层、预后评估和治疗效果评估。该研究还突出了儿童AML的独特性，并促进了新免疫疗法和靶向治疗策略的发展。© 2023. 作者，独家授权Springer-Verlag GmbH Germany，属于Springer Nature。

Acute myeloid leukemia (AML) is a common leukemia with low cure rate and poor prognosis among pediatric patients. The regulation of AML immune microenvironment and methylation remains to be explored. Pediatric and adult AML patients differ significantly in epigenetic factors, and the efficiency of treatment modalities varies between the two groups of patients.We collected mRNA, miRNA and DNA methylation data from pediatric AML patients across multiple databases. Differentially expression genes were identified, and a gene-miRNA regulatory network was constructed. Prognostic risk models were established by integrating LASSO and Cox regression, and a nomogram was generated. Based on this model, we investigated tumor-infiltrating immune cells and cell communication, analyzing the biological functions and pathways associated with prognostic factors. Furthermore, the relationships between all prognostic factors and gene modules were explored, and the impact of these factors on treatment modalities was determined.We developed an efficient prognostic risk model and identified HOXA9, SORT1, SH3BP5, mir-224 and mir-335 as biomarkers. We validated these findings in an external dataset and observed a correlation between age and risk in pediatric patients. AML samples with lower risk scores have a better prognosis and higher expression of immune-upregulated biomarkers, and have lower immune scores. Furthermore, we detected discrepancies in immune cell infiltration and interactions between high- and low-risk group samples, which affected the efficacy of immunotherapy. We evaluated all prognostic factors and predicted the effect of immunotherapy and medicine.This study comprehensively investigated the role of methylation signature genes in pediatric AML at the level of genomes and transcriptomes. The research aims to enhance the risk stratification, prognosis evaluation and assessment of treatment effectiveness of AML patients. This study also highlight the uniqueness of pediatric AML and foster the development of new immunotherapy and targeted therapy strategies.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.