急性髓系白血病（AML）是一种分子异常和临床结果多样的血液癌症。铁平衡和细胞死亡通路在癌症发病机制中起着关键作用，包括AML。本研究的目的是检查与AML中涉及铁相关细胞死亡和凋亡通路的基因的临床意义，旨在提供有预后意义并促进有针对性的治疗干预的洞察力。我们整合了来自多个数据集（包括TCGA-LAML和GSE71014）的基因表达谱，临床信息和分子变化。我们的分析确定了特定的AML分子亚型，其表达铁相关凋亡和细胞死亡通路基因与不同结局、免疫细胞浸润模式和靶向治疗的药物敏感性有关。我们进一步开发了基于四个基因的风险模型，在训练组和验证组中均显示出有希望的预后价值，表明该模型在AML的临床决策和风险分层中具有潜力。随后，Western blot分析显示，在CD4表达水平被抑制后，C-Myc和CyclinD1的表达水平显著降低。这些发现强调了铁相关细胞死亡通路作为AML预后生物标志物和治疗靶点的潜力，并为进一步研究铁平衡、凋亡调控和骨髓微环境中的免疫调节之间的分子机制奠定了基础。版权所有 © 2023 Li, Lin, Zhu, Zhou, Fan, Zhou, Mu, Sheng and Ouyang.

Acute myeloid leukemia (AML) is a blood cancer that is diverse in terms of its molecular abnormalities and clinical outcomes. Iron homeostasis and cell death pathways play crucial roles in cancer pathogenesis, including AML. The objective of this study was to examine the clinical significance of genes involved in iron-related cell death and apoptotic pathways in AML, with the intention of providing insights that could have prognostic implications and facilitate the development of targeted therapeutic interventions. Gene expression profiles, clinical information, and molecular alterations were integrated from multiple datasets, including TCGA-LAML and GSE71014. Our analysis identified specific molecular subtypes of acute myeloid leukemia (AML) displaying varying outcomes, patterns of immune cell infiltration, and profiles of drug sensitivity for targeted therapies based on the expression of genes involved in iron-related apoptotic and cell death pathways. We further developed a risk model based on four genes, which demonstrated promising prognostic value in both the training and validation cohorts, indicating the potential of this model for clinical decision-making and risk stratification in AML. Subsequently, Western blot analysis showed that the expression levels of C-Myc and CyclinD1 were significantly reduced after CD4 expression levels were knocked down. The findings underscore the potential of iron-related cell death pathways as prognostic biomarkers and therapeutic targets in AML, paving the way for further research aimed at understanding the molecular mechanisms underlying the correlation between iron balance, apoptosis regulation, and immune modulation in the bone marrow microenvironment.Copyright © 2023 Li, Lin, Zhu, Zhou, Fan, Zhou, Mu, Sheng and Ouyang.