Figure 7.
GLUT1 and OXPHOS inhibition has synergistic antileukemic efficacy in human AML cells. Assessment of synergistic effects between pharmacological inhibition of GLUT1 (BAY-876) and OXPHOS (IACS-010759) in (A) THP-1 and (B) Mono Mac 6. Quantification of viable cell counts after 72-hour treatment with increasing doses of BAY-876 alone (orange) or together with 20 nM IACS-010759 (purple) assessed by flow cytometry. Data were normalized to corresponding DMSO-treated controls. (C) Viability of primary AML samples treated ex vivo with indicated concentrations of BAY-876 alone (orange) or together with 100 nM IACS-010759 (purple), normalized to corresponding DMSO-treated controls. (D) Stratification of AML patients into “responders” and “nonresponders.” (E) Viability of CD34+ normal bone marrow cells relative to primary AML cells. (F) Comparison of viability in RUNX1-mutated vs wild-type adult AML after dual treatment with BAY-876 and 100 nM IACS-010759. (D-F) Data were normalized to viability corresponding to 100 nM IACS-010759 treatment alone and are shown as mean ± SD (n = 3-4). Synergistic effects have been marked with the letter “S.” Statistical testing was performed by unpaired 2-tailed Student t test; ∗P < .05. Refer to supplemental Figures 6-9 and supplemental Table 4.

GLUT1 and OXPHOS inhibition has synergistic antileukemic efficacy in human AML cells. Assessment of synergistic effects between pharmacological inhibition of GLUT1 (BAY-876) and OXPHOS (IACS-010759) in (A) THP-1 and (B) Mono Mac 6. Quantification of viable cell counts after 72-hour treatment with increasing doses of BAY-876 alone (orange) or together with 20 nM IACS-010759 (purple) assessed by flow cytometry. Data were normalized to corresponding DMSO-treated controls. (C) Viability of primary AML samples treated ex vivo with indicated concentrations of BAY-876 alone (orange) or together with 100 nM IACS-010759 (purple), normalized to corresponding DMSO-treated controls. (D) Stratification of AML patients into “responders” and “nonresponders.” (E) Viability of CD34+ normal bone marrow cells relative to primary AML cells. (F) Comparison of viability in RUNX1-mutated vs wild-type adult AML after dual treatment with BAY-876 and 100 nM IACS-010759. (D-F) Data were normalized to viability corresponding to 100 nM IACS-010759 treatment alone and are shown as mean ± SD (n = 3-4). Synergistic effects have been marked with the letter “S.” Statistical testing was performed by unpaired 2-tailed Student t test; ∗P < .05. Refer to supplemental Figures 6-9 and supplemental Table 4.

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