Identifying an immunogenic cell death-related gene signature and HSPA6 infers adverse prognosis in acute myeloid leukemia.

Immunogenic cell death (ICD) represents a specific form of regulatory cell death that initiates an adaptive immune response. We aimed to investigate the significance of immunogenic cell death-related genes (ICDGs) in AML, utilizing a combination of bioinformatics analysis, consensus clustering, functional enrichment analysis, and experimental validation in cell lines and animal models. Here, we identified 34 ICDGs, and single-cell analysis indicated that CD8+ T cells and NK cells exhibited gene expression patterns closely associated with ICD. Consensus clustering revealed two distinct subtypes of AML (ICD-high and ICD-low), with the former correlating with more favorable clinical outcomes and heightened infiltration of immune cells. A predictive model was established through LASSO regression, yielding a risk signature comprising six key ICDGs (FGFBP2, GZMB, ALPK2, NELL2, OPTN, FCGR2B), which successfully categorizes patients into high-risk and low-risk cohorts based on overall survival outcomes. Notably, HSPA6 emerged as a critical ICDG, with its knockdown in OCI-AML3 cells significantly inhibiting proliferation and inducing apoptosis, suggesting its potential as a therapeutic target. In summary, our research emphasizes the importance of ICD-related genes in predicting the prognosis of AML and initiates the development of a prognostic risk signature that may pave the way for personalized treatment strategies while highlighting the need for further validation and exploration of HSPA6 in AML.