Influência de polimorfismos no gene IL10 no prognóstico clínico de pacientes pediátricos com Leucemia Linfoblástica Aguda

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world, characterized by exacerbated clonal proliferation of lymphoblasts and accumulation of leukemic clones in the bone marrow. Its etiology is still poorly understood, however, some immunogenetic factors are associated with its development, including the deficient production of interleukin-10 (IL-10) related to the presence of genetic mutations. Therefore, the objective of the present study was to evaluate the influence of single nucleotide variants (SNVs) in the IL10 gene (rs1800871, rs1808796 and rs3021094) in pediatric patients with ALL, in addition to describing the relationship of SNVs with clinical and laboratory manifestations and serum concentrations. of IL-10. A case-control study was carried out with 102 patients with ALL and 177 healthy individuals. The DNA samples were genotyped by Real-Time PCR (qPCR). IL-10 concentrations in bone marrow and peripheral blood were quantified by flow cytometry (CBA). Clinical and demographic data demonstrated that the ALL B subtype is the most common among patients with ALL and the median age was 7 years. Males had a higher overall frequency for both groups and 52% of patients with ALL had some type of comorbidity. Approximately 52% of patients with ALL relapsed and 34% died during treatment. The IL10 G/T rs3021094 genotype ([OR: 0.16; 95% CI: 0.07–0.37, p= 0.003]) was associated with protection against relapse and death in patients with ALL. The SNVs rs1800871 and rs1800896 of the IL10 gene were also associated with protection against death, however the SNV rs1800896 was shown to be an indicator of risk for relapse in patients with ALL. However, no association was observed between the variants and concentration of the cytokine IL-10. In conclusion, our study demonstrated that the mutated alleles G>T (rs3021094) and T>C (rs1800896) were highly frequent in patients with ALL, which suggests that these variants may serve as prognostic markers. However, future studies must be carried out to better elucidate the role of these SNVs in ALL.