ALL-232: Genetic Variants of Tumor Necrosis Factor α and Interleukin-10 in Childhood and Adult Acute Lymphoblastic Leukemia

Context Interleukin-(IL)10 and tumor necrosis factor (TNF) a have a significant role in malignancies. Genes encoding these cytokines are linked with different levels of gene transcription. Objective Analyzing IL-10 and TNFα gene polymorphisms and their contribution to ALL prognosis and survival. Design This prospective observational study was conducted from June 2017 until Oct 2019. Setting Oncology Center Mansoura University, Egypt. Patients or other participants We genotyped 64 children and 76 adult ALL patients for IL-10-1082A > G and TNFα-308G > A polymorphisms in the gene promoter region. We used polymerase chain reaction (restriction fragment length polymorphism method) for the molecular analysis. Results Pediatric ALL patients showed TNFα A allele and IL-10 A allele, which were associated with older age (p = 0.04, 0.03), extramedullary disease (p = 0.04, 0.001), and carried Philadelphia chromosome (p = 0.02, 0.001), compared to the G allele, respectively. IL-10-1082AA and TNF 308AA genotypes carried on the Ph-positive chromosome were associated with a longer time to CR and a higher rate of relapse than other genotypes. The IL-10 (GG) genotype was associated with significant improvement of OS compared to IL-10 (GA) and (AA) genotypes (p = 0.026). The adult ALL patients carrying the A allele of TNFα had a higher rate extramedullary disease (p = 0.009) and a higher rate of relapse (p = 0.003). Also, we found increased frequency of the IL-10-A allele with advanced age (p = 0.03), lower Hb level (p = 0.04), increased extramedullary disease (p = 0.001), and Ph chromosome positivity (p = 0.001), which resulted in longer time to CR (p = 0.003) and high relapse rate (p = 0.002). IL-10 (AA) and TNFα (AA) genotype patients were associated with extramedullary disease, carried the Ph-positive chromosomal abnormality, and had a higher rate of relapse than other genotypes among adult ALL patients. Patients with IL-10 (GG) and TNFα (GG) genotypes did not show significant improvement of OS and RFS by Kaplan-Meier curves (p > 0.05) compared to other genotypes. Conclusion IL-10 (AA) and TNFα (AA) were associated with poor prognostic factors in childhood and adulthood ALL. This might modulate the risk, overall survival, and relapse-free survival among ALL patients.