Upregulation of NFS1 and downregulation of GSDMD as prognostic biomarkers in acute myeloid leukemia: implications for diagnosis and therapeutic strategies

BACKGROUND: Despite advances in the treatment of Acute Myeloid Leukemia (AML), the predictive 5-year overall survival rate is still poor not exceeding 20%. Most patients develop relapse partly due to resistance mechanisms to classical cell death programs. Currently, cytogenetic markers play a crucial role in the early diagnosis, prognostic classification, and therapy selection for AML. Yet, there is a pressing need for the discovery of novel AML biomarkers for a better understanding of the disease's molecular mechanisms, diagnosis, prognosis assessment, and personalized therapeutic response. The role of cell death-related genes in driving AML progression and spread remains inadequately explored. Among these, ferroptosis and pyroptosis are emerging as critical mechanisms of programmed cell death that are often dysregulated in cancer. METHODS: We recruited 100 newly diagnosed AML patients and 40 healthy matched individuals. Using reverse transcription-quantitative PCR analysis, we assessed the expression levels of NFS1 and Gasdermin D (GSDMD). RESULTS: Our findings revealed significant NFS1 upregulation (P < 0.0001) and GSDMD downregulation (P < 0.0001) in AML patients compared to healthy controls. Following treatment, we observed a significant downregulation of NFS1 expression (P < 0.001) and upregulation of GSDMD (P < 0.001). Furthermore, higher pretreatment levels of NFS1 and lower pretreatment levels of GSDMD correlated with poor prognosis (P < 0.001) and decreased one-year survival (P < 0.001). CONCLUSION: Our study suggests that NFS1 and GSDMD may serve as early diagnostic and prognostic markers in AML, offering potential targets for improved therapeutic strategies.