Atividade das enzimas que degradam nucleotídeos e nucleosídeo da adenina em leucemia linfoblástica aguda B derivada

Abstract

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a neoplasm characterized by an anomalous clonal proliferation of B lymphoid precursor cells and predominance in pediatric patients. BCP-ALL promotes the deregulation of physiological and immunological processes. Among the immune processes modulators, ATP, ADP, AMP and adenosine stand out. The extracellular concentrations of these nucleotides are regulated by the ectoenzymes E- NTPDase (CD39), E-5'-NT (CD73), and ecto-adenosine deaminase (E-ADA). This study aimed to evaluate the activities of E-NTPDase and E-ADA in peripheral lymphocytes, measure the expression of CD39 and CD73 in peripheral blood, evaluate the activities of NTPDase, ADA and XO, the levels of soluble nucleotides and nucleosides of adenine and the cytokines in the serum, in order to evaluate the immune response in BCP-ALL patients. Thirty-two patients were evaluated at diagnosis (D0), 14 patients 15 days after the beginning of the treatment (D15), and 34 healthy individuals in the control group (C). The activities of ectonucleotidases and soluble enzymes NTPDase and ADA were determined on isolated peripheral lymphocytes and serum, respectively. Flow cytometry method was used to evaluate the expressions of CD39 and CD73 in lysed whole blood and the levels of cytokines in the serum. The nucleotides and nucleosides levels were evaluated in serum by HPLC method. Concerning to the activity on lymphocytes, E-NTPDase (ADP substrate) was reduced in D15 group, while E-ADA activity was increased on D0 and on D15 when compared to the control group. The activities of NTPDase (ATP and ADP substrate) and XO in serum were decreased on D0, whereas ADA activity was significantly increased on D0 compared to the control group. D15 group showed increase on NTPDase and XO activities compared to D0 group. CD39 and CD73 expression levels were distinct according to the cell maturation degree. On D0, lymphoblasts showed lower CD39 and higher CD73 expressions in relation to lymphocytes from the same group. Serum purine levels of inosine and xanthine were significantly increased, whereas of hypoxanthine was decreased on D0. The cytokines IL-6, IL-17 and IL-10 levels were significantly increased on D0 when compared to control group. The results showed an inflammatory status of BCP-ALL at diagnosis, and a possible modulation of the purinergic signaling system and of cytokines on neoplasic lymphocytes, which may influence in the immunosuppression status and the changes in the immune response, making the neoplasic cell proliferation possible. Complementary studies may identify individual patient characteristics in the purinergic signalling, to assist in the choice of a more specific therapy.