Prognostic significance of inflammatory cytokine polymorphisms in AML: a study of IFNG, TNFA, and IL1B polymorphisms.

BACKGROUND

Inflammatory cytokines influence the pathogenesis and progression of acute myeloid leukaemia (AML), not only by shaping the leukemic microenvironment, but also by supporting leukaemia stem cell survival and resistance to therapy. We, therefore, investigated the associations between the cytokine polymorphisms IFNG+874 A/T, TNFA-857 C/T, and IL1B -31 C/T and AML outcomes, as well as their influence on clinical features.

RESULTS

Ninety-three patients with AML and 117 healthy controls were analysed. The T allele of TNFA - 857 C/T (i.e., the high-expression allele) was observed at a significantly higher frequency in the patients with AML vs. the controls (AML vs. control = 24.7% vs. 16.2%, p = 0.04). Patients with the high-expression TT genotype had shorter overall survival (TT vs. CC = 46.0 vs. 224.1 months, p < 0.001). Patients with the high-expression non-CC genotype relapsed more frequently than those with the low-expression CC genotype (relapse vs. non-relapse = 55.8% vs. 26.9%, p = 0.01). No significant associations were observed for the IFNG + 874 A/T and IL1B -31 C/T polymorphism.

CONCLUSION

TNFA - 857 C/T polymorphisms can influence patient susceptibility to AML, as well as its prognosis. This suggests a link between chronic inflammation and leukemogenesis, as well as the potential value of TNFA genotyping in risk assessments.