Caracterização das microvesículas circulantes e seu potencial uso como biomarcador no diagnóstico e tratamento de pacientes com LMC

Abstract

Chronic Myeloid Leukemia is a hematologic malignancy that affects cells of the myeloid lineage. The vast majority of patients have the Philadelphia chromosome, which produces a hybrid protein with increased tyrosine kinase activity. Treatment is performed with tyrosine kinase inhibitors, which block oncoprotein expression. The inhibitors act in the control of immature cells, being of extreme importance the molecular monitoring of the patients. In recent years, the importance of microvesicles has been studied, as they can be used as a marker of relapse during the disease, and provide information on drug resistance. Since they play an important role in intercellular communication and studies indicate that their release increases in pathological processes. The aim of this study was to characterize the profile of microvesicles in patients with Chronic Myeloid Leukemia at diagnosis and during the first year of treatment. This research is a descriptive and exploratory study, of the bidirectional type. Thirty patients of both sexes were recruited, divided into two groups: 15 patients with CML, and 15 blood donors, as a control group. Peripheral blood samples were collected from patients in four moments (at diagnosis, in cytoreduction, 3 months and 6 months of treatment with tyrosine kinase inhibitors), while in the control group peripheral blood was collected in only one moment. The samples were processed and phenotypic quantifications and analyzes were performed through the flow cytometry technique using surface markers to identify progenitor cells, myeloid cells, leukocytes, dendritic cells, monocytes, neutrophils, T cells, B cells, platelets, erythrocytes and endothelial cells. The research results showed that microvesicles released from progenitor cells (CD34), neutrophils (CD16 and CD66), erythrocytes (CD235a), dendritic cells (CD11c) and endothelial cells (CD51/61) are significantly more expressed in patients with CML than diagnosis compared to the control group. However, at the beginning of treatment with tyrosine kinase inhibitors, a decrease in the amount of microvesicles released from progenitor cells, myeloid cells, leukocytes, dendritic cells, monocytes, neutrophils, T cells, B cells, erythrocytes and endothelial cells can be observed. In addition, changes in the interactions between populations of microvesicles can be observed over the course of patient follow-up. Future investigations are needed with a larger number of participants and with longer follow-up, in order to validate these findings