Caracterização dos polimorfismos nos genes do complexo inflamassoma na leucemia linfoblástica aguda

Abstract

Inflammasomes are crucial mediators of the inflammatory response, and certain polymorphisms in genes of this complex can influence the transcription of target genes and contribute to the development and progression of hematologic malignancies. However, studies exploring this relationship in acute lymphoblastic leukemia (ALL) are scarce. Therefore, we performed a literature review on the role of inflammasomes in leukemias and a systematic review with meta-analysis on the role of the IL1B -511 polymorphism in the development of hematologic malignancies. In addition, a casecontrol study with 210 patients with ALL and 205 healthy individuals was performed to describe the role of AIM2 rs1103577, IFI16 rs1633266, CASP1 rs570685 and CARD8 rs2043211A polymorphisms in the risk or protection for ALL and clinical outcome. Furthermore, we also evaluated its influence on serum concentrations of the cytokines IL-1β, IL-6, IL-10, IL-12p70 and TNF. Genotyping was performed using the Real-Time Polymerase Chain Reaction (qPCR) technique using Taqman probes and cytokine measurement using the Cytometric Bead Array (CBA) technique. In our systematic review and meta-analysis, we did not identify an association between the IL1B -511 polymorphism and the risk of any hematologic neoplasia. On the other hand, in our experimental study, the overdominant model of the AIM2 rs1103577 polymorphism was associated with a lower risk of developing acute lymphoblastic leukemia in our population (ORadj: 0.56 95% CIadj: 0.35–0.90, padj=0.003), as well as the codominant model with a lower chance of death (ORadj: 0.47, 95% CIadj: 0.24–0.93, padj=0.018). We did not observe an association between the genotypes of the polymorphisms under study in the secretion of cytokines when evaluated in the bone marrow and peripheral blood. Finally, we highlight that this is the first study that investigated the relationship of AIM2 rs1103577, IFI16 rs1633266, CASP1 rs570685 and CARD8 rs2043211 polymorphisms in the development and clinical outcome of patients diagnosed with ALL from the Brazilian Amazon. A deeper understanding of the genetic variations of the inflammasome complex genes will allow us to identify molecular biomarkers of early prognosis and contribute to the improvement of treatments for the disease.