Lymphocytes from B-acute lymphoblastic leukemia patients present diferential regulation of the adenosinergic axis depending on risk stratifcation

• Autor(a) principal: Nunes, Vitoria Brum da Silva
• Data de Publicação: 2022
• Outros Autores: Dias, Camila kehl, Scholl, Juliete Nathali, Sant' Ana, Alexia Nedel, Dias, Amanda de Fraga, Farias, Mariela Granero, Alegretti, Ana Paula, Sosnoski, Monalisa, Daudt, Liane Esteves, Michalowski, Mariana Bohns, Battastini, Ana Maria Oliveira, Paz, Alessandra Aparecida, Figueiró, Fabrício
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/256344
• topic: Leucemia-linfoma linfoblástico de células precursoras; Sistema imunitário; Nucleotídeos de adenina; Nucleosideos; Nucleotídeos; Adenina; Citocinas; Adenosina; Subpopulações de linfócitos; B-cell acute lymphoblastic leukemia; Ectonucleotidases; Immunomodulators; Lymphocyte subpopulations

Purpose Although risk-stratifed chemotherapy regimens improve B-cell acute lymphoblastic leukemia (B-ALL) clinical outcome, relapse occurs in a signifcant number of cases. The identifcation of new therapeutic targets as well as prog nostic and diagnostic biomarkers can improve B-ALL patients’ clinical outcomes. Purinergic signaling is an important pathway in cancer progression, however the expression of ectonucleotidases and their impact on immune cells in B-ALL lacks exploration. We aimed to analyze the expression of ectonucleotidases in B-ALL patients’ lymphocyte subpopulations. Methods Peripheral blood samples from 15 patients diagnosed with B-ALL were analyzed. Flow cytometry was used to analyze cellularity, expression level of CD38, CD39, and CD73, and frequency of CD38+∕CD73+, and CD39+∕CD73+ in lymphocyte subpopulations. Plasma was used for cytokines (by CBA kit) and adenine nucleosides/nucleotides detection (by HPLC). Results Comparing B-ALL patients to health donors, we observed an increase of CD4+and CD8+T-cells. In addition, a decrease in CD38 expression in B and Treg subpopulations and an increase in CD39+ CD73+ frequency in Breg and CD8+ T-cells. Analyzing cytokines and adenine nucleosides/nucleotides, we found a decrease in TNF, IL-1β, and ADO concentrations, together with an increase in AMP in B-ALL patients’ plasma. Conclusion: As immunomodulators, the expression of ectonucleotidases might be associated with activation states, as well as the abundance of diferent cellular subsets. We observed a pro-tumor immunity expression profle in B-ALL patients at diagnosis, being associated with cell exhaustion and immune evasion in B-ALL.