Avaliação molecular de AURKA, AURKB e PLK1 no processo de leucemogênese em pacientes portadores de Leucemia Mieloide aguda no estado do Ceará

Abstract

Acute myeloid leukemia (AML) is one of the most aggressive types of leukemia, represented by the clonal proliferation of myeloid precursors, which mainly promotes quantitative and differentiation alterations, as well as suppression of normal hematopoiesis. Throughout leukemogenesis, modifications may occur in several elements that make up cellular signaling pathways, among which we highlight the AURKA, AURKB, and PLK1 proteins, which are directly related to cell cycle control and cell proliferation. This study investigated the hematological profile and the expression of the AURKA, AURKB, and PLK1 genes in a cohort of individuals with AML, in order to understand their roles in the pathophysiology of the disease. The analyses revealed a significant underexpression of AURKA in the bone marrow of patients compared to the control group (p = 0.0254) and an overexpression of PLK1 both in bone marrow (p < 0.0001) and in peripheral blood (p = 0.0144). In contrast, AURKB did not show a significant difference. Our data suggest that the low expression of AURKA is associated with the suppression of normal hematopoiesis due to the reduction of healthy blast cells and/or the quiescent state of the cells as a result of leukemic infiltration, which rely on alternative mechanisms to proliferate, possibly mediated by the activity of PLK1, which in our study showed increased expression. Furthermore, our results also point to PLK1 as a potential biomarker for the presence of the disease, since its overexpression did not differ with respect to gender, risk stratification, or age of the individuals. Finally, survival analyses indicate that AURKA expression in the bone marrow is associated with a protective factor and increased patient survival, and that those with higher expression of the three target genes had a lower mortality rate (p = 0.043).