TY - EJOU AU - Silvano, Angela AU - Menegazzi, Giulio AU - Peppicelli, Silvia AU - Mancini, Caterina AU - Biagioni, Alessio AU - Tubita, Alessandro AU - Tusa, Ignazia AU - Ruzzolini, Jessica AU - Lulli, Matteo AU - Rovida, Elisabetta AU - Sbarba, Persio Dello TI - Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction T2 - Oncology Research PY - 2021 VL - 29 IS - 1 SN - 1555-3906 AB - This study was directed to deepen the effects of nutrient shortage on BCR/Ablprotein expression and signaling in chronic myeloid leukemia (CML) cells. The backbone of the study was cell culture in medium lacking glucose, the consumption of which we had previously shown to drive BCR/Ablprotein suppression, and glutamine, the other main nutrient besides glucose. In this context, we focused on the role of lactate, the main by-product of glucose metabolism under conditions of rapid cell growth, in particular as a modulator of the maintenance of CML stem/progenitor cell potential, a crucial determinant of disease course and relapse of disease. The results obtained indicated that lactate is a powerful surrogate of glucose to prevent the suppression of BCR/Abl signaling and is therefore capable to maintain BCR/Abl-dependent CML stem/progenitor cell potential. A number of metabolism-related functional and phenotypical features of CML cells were also determined. Among these, we focused on the effect of lactate on oxygen consumption rate, the dependence of this effect on the cell surface lactate carrier MCT-1, and the relationship of the lactate effect to pyruvate and to the activity of mitochondrial pyruvate carrier. KW - Chronic myeloid leukemia (CML); Nutrient shortage; Lactate; Stem cell potential; Acidosis; MCT-1 DO - 10.3727/096504022X16442289212164