Open Access
ARTICLE
Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction
Angela Silvano*†1, Giulio Menegazzi*1, Silvia Peppicelli*1,
Caterina Mancini*, Alessio Biagioni*, Alessandro Tubita*, Ignazia Tusa*, Jessica Ruzzolini*, Matteo Lulli*, Elisabetta Rovida*, Persio Dello Sbarba*
* Department of Experimental and Clinical Biomedical Sciences “Mario Serio,” Careggi Hospital, Università degli Studi di Firenze,
Florence, Italy
† Department of Health Sciences, Division of Obstetrics and Gynecology, Careggi Hospital, Università degli Studi di Firenze,
Florence, Italy
Oncology Research 2021, 29(1), 33-46. https://doi.org/10.3727/096504022X16442289212164
Abstract
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.
Keywords
Cite This Article
Silvano, A., Menegazzi, G., Peppicelli, S., Mancini,
. C., Biagioni, A. et al. (2021). Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction.
Oncology Research: Featuring Preclinical and Clinical Cancer Therapeutics, 29(1), 33–46.