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Acidification in the microenvironment plays an immunosuppressive role and mediates the protonation of drugs, affecting their cell permeability ( 2.4 Association between increased glycolysis with clinical response and survival rates in ALs Despite the strong evidence that glycolytic metabolism can promote chemoresistance in primary leukemic cells from non-responders and/or multiresistant cell lines, recent advances in metabolomics platforms have allowed further investigation into tumor metabolism at the systemic level in patients with acute leukemia ( 3 Chemoresistance-induced mitochondrial function in ALs Mitochondria allow metabolic adaptation to various stress conditions as they are an integrating center of important cellular processes that include energy production through OxPhos, redox signaling, anabolic and catabolic reactions, epigenetic regulation, cell self-renewal and differentiation, initiation, and run-time programmed cell death (PCD) ( + cells and peripheral blood mononuclear cells (PBMCs) ( 3.1 Mitochondria as a promoter of chemoresistant AML and ALL cells Various publications have described the role of mitochondrial activity in resistance or sensitivity to chemotherapy treatment in ALs