Genetic predisposition meets cytokine imbalance: the influence of TNF-α (-308) polymorphism and TGF-β levels in pediatric acute lymphoblastic leukemia in Egypt

Evading apoptosis fuels the aggressive nature of acute lymphoblastic leukemia (ALL). This study explored the potential roles of TNF-α, a pro-apoptotic cytokine, and TGF-β, a pro-proliferative factor, in the risk of developing ALL in Egyptian children. We investigated the TNF-α rs1800629 polymorphism and serum TGF-β levels in 100 ALL patients and 100 healthy controls. Notably, specific variations in TNF-α (GA, AA genotypes, and dominant model) were associated with an increased risk of ALL, suggesting impaired apoptosis. Conversely, ALL patients exhibited significantly lower TGF-β levels, potentially promoting uncontrolled proliferation. Our findings suggest that lower TGF-β and the TNF-α (-308) dominant model are associated with an increased risk of ALL. Additionally, TGF-β demonstrated exceptional accuracy (AUC 0.995) as a potential marker, with 100% sensitivity and 96% specificity. These findings suggest that TNF-α and TGF-β may be associated with ALL susceptibility, though further research with larger and more diverse populations is necessary to confirm these results.