Lymphocytes from B-acute lymphoblastic leukemia patients present differential regulation of the adenosinergic axis depending on risk stratification.

PURPOSE: Although risk-stratified chemotherapy regimens improve B-cell acute lymphoblastic leukemia (B-ALL) clinical outcome, relapse occurs in a significant number of cases. The identification of new therapeutic targets as well as prognostic 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 [Formula: see text], and [Formula: see text] 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-1ß, 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 different cellular subsets. We observed a pro-tumor immunity expression profile in B-ALL patients at diagnosis, being associated with cell exhaustion and immune evasion in B-ALL.

Metabolic rewiring in melanoma drug-resistant cells.

Several evidences indicate that melanoma, one of the deadliest types of cancer, presents the ability to transiently shift its phenotype under treatment or microenvironmental pressure to an invasive and treatment-resistant phenotype, which is characterized by cells with slow division cycle (also called slow-cycling cells) and high-OXPHOS metabolism. Many cellular marks have been proposed to track this phenotype, such as the expression levels of the master regulator of melanocyte differentiation (MITF) and the epigenetic factor JARID1B. It seems that the slow-cycling phenotype does not necessarily present a single gene expression signature. However, many lines of evidence lead to a common metabolic rewiring process in resistant cells that activates mitochondrial metabolism and changes the mitochondrial network morphology. Here, we propose that mitochondria-targeted drugs could increase not only the efficiency of target therapy, bypassing the dynamics between fast-cycling and slow-cycling, but also the sensitivity to immunotherapy by modulation of the melanoma microenvironment.