Leucemia linfocítica crônica: avaliação da expressão gênica da proteína quinase AKT, de microRNAs e dos níveis plasmáticos de IL-4 relacionados com a patogênese da doença

Abstract

Chronic lymphocytic leukemia (CLL) is recognized by heterogeneous clinical course and can not be accurately predicted by clinical staging systems. This leads to the investigation of prognostic markers that can add predictive value to staging systems. The present study aimed to evaluate markers with prognosis potential focusing on AKT protein kinase and microRNAs (miRNAs ou miRs) expression and on quantification of IL-4 plasma levels in patients with CLL compared to controls. We evaluated 80 patients diagnosed with CLL at the Hematology Service of the Hospital das Clínicas of the Federal University of Minas Gerais. As a control group, 75 individuals, apparently healthy and without previous history of leukemia, were also evaluated. The AKT and microRNAs gene expression were assessed by quantitative PCR (qPCR) and IL-4 plasma levels determination by the ELISA immunoassay. There was a significant increase in AKT gene expression in patients when compared to the controls (p=0,017). When the patients were stratified according to the Binet groups, a significant difference was observed between the groups, being this protein kinase most expressed in the B+C group (p=0,013). As for miRNA expression, miR-let-7b and miR-26a were reduced in CLL patients. However, no significant differences were observed in these microRNAs gene expression when comparing the patients between the Binet (A versus B+C) groups. IL-4 had a higher plasma concentration in controls when compared to patients (p<0,001) and there were no significant differences when comparing the Binet groups. The reduction of IL-4 in patients can be attributed, in part, to the reduction of T lymphocytes in these patients. The AKT protein kinase is involved in the signaling cascade that occurs with activation of BCR receptor that leads to increased survival of lymphocytes in CLL and protection against the process of cell death induction. Increased AKT protein kinase and the reduction of miR-let7b and miR-26a, both tumor suppressors, in CLL patients may explain increased lymphocyte survival in these patients and could be used as poor prognostic biomarkers.