Figure 6.
ATO-resistant cells are metabolically heterogeneous, and the in vivo effect of glycolytic inhibition by 2-DG reduces leukemic burden in the APL mouse model. (A) The extracellular acidification rate (ECAR) and glycolytic potential of NB4 naïve, NB4EV-AsR1, and UF1 cell lines were assessed in real time by using a Seahorse extracellular flux analyzer. (B) Viability of the sensitive and resistant cell lines after 48 hours of glycolytic inhibitor ATO and 2-DG (ATO, 2 µM; 2-DG, 5 mM; n = 4). (C) Schematic representation of the APL transplantable mouse model and treatment plan. Mice were euthanized on day 22 and examined for the presence of leukemic cells (CD117+Gr1+) in peripheral blood (PB) and PML-RARA transcript levels in bone marrow. All error bars represent mean ± SEM of 4 independent experiments. **P ≤ .01; ***P ≤ .001. IP, intraperitoneal; ns, not significant.

ATO-resistant cells are metabolically heterogeneous, and the in vivo effect of glycolytic inhibition by 2-DG reduces leukemic burden in the APL mouse model. (A) The extracellular acidification rate (ECAR) and glycolytic potential of NB4 naïve, NB4EV-AsR1, and UF1 cell lines were assessed in real time by using a Seahorse extracellular flux analyzer. (B) Viability of the sensitive and resistant cell lines after 48 hours of glycolytic inhibitor ATO and 2-DG (ATO, 2 µM; 2-DG, 5 mM; n = 4). (C) Schematic representation of the APL transplantable mouse model and treatment plan. Mice were euthanized on day 22 and examined for the presence of leukemic cells (CD117+Gr1+) in peripheral blood (PB) and PML-RARA transcript levels in bone marrow. All error bars represent mean ± SEM of 4 independent experiments. **P ≤ .01; ***P ≤ .001. IP, intraperitoneal; ns, not significant.

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