Abstract
Background and Objectives: A thorough comprehension of the essential molecules and related processes underlying the carcinogenesis, proliferation, and recurrence of acute myeloid leukemia (AML) is crucial. This study aimed to investigate the expression levels, diagnostic and prognostic significance and biological roles of Bcl-2-associated athanogene 4 (BAG4) in AML carcinogenesis. Materials and Methods: Gene expression profiles were analyzed using publicly available datasets, particularly GSE9476 and TCGA, using tools such as GEO2R, GEPIA2, UALCAN and TIMER2.0. The immune infiltration correlation was examined using the GSCA platform, while the function of BAG4 at the single-cell level was analyzed via CancerSEA. Protein-protein and gene-gene interaction networks were constructed using STRING and GeneMANIA, and enrichment analyses were performed using GO, KEGG and DAVID. Expression validation was performed using RT-qPCR in HL-60 (AML) and HaCaT (normal) cells, and ROC curve analysis evaluated the diagnostic accuracy. Results: BAG4 was significantly overexpressed in AML tissues and cell lines compared with healthy controls. High BAG4 expression was associated with poor overall survival and strong diagnostic power (AUC = 0.944). BAG4 was positively associated with immune cell infiltration and negatively associated with CD4+/CD8+ T and NK cells. At the single-cell level, BAG4 was associated with proliferation, invasion, and DNA repair functions. Functional network analysis showed that BAG4 interacted with apoptosis and necroptosis-related genes such as BCL2, BAG3 and TNFRSF1A and was enriched in pathways such as NF-κB, TNF signaling and apoptosis. Conclusions: BAG4 is overexpressed in AML and is associated with adverse clinical outcomes and immune modulation. It may play an important role in leukemogenesis by affecting apoptotic resistance and immune evasion. BAG4 has potential as a diagnostic biomarker and treatment target in AML, but further in vivo and clinical validation is needed.