Figure 3.
Effects of the GLS inhibitor CB-839, alone or in combination with the glycolytic inhibitor 3PO on hematologic parameters in vivo. (A) Experimental setup. Drug treatment started after 4 weeks of engraftment, n = 12 mice per group. (B) Body weight monitoring during the course of the study, as an indicator of toxicity. (C) Spleen weight of the mice at the end of the treatment. (D) Top: effects on blood counts measured at week 4 of the treatment and at week 6. Middle: VF;GFP chimerism of different cell types in peripheral blood, calculated by % of GFP+ cells in each population analyzed by flow cytometry. From left to right: erythrocytes (Ter119+), platelets (CD61+), neutrophils (CD11b+ Gr1+), B-cells (B220+), and T-cells (CD3+). Bottom: red blood cell (RBC) count, MCV, and mean corpuscular hemoglobin (MCH) of RBCs. The area colored in gray depicts the normal range expected for WT mice. The plots represent the mean ± SEM. 2-way ANOVA for panels B,D or 1-way ANOVA for panel C with multiple comparisons with the vehicle group (Fisher LSD test) were performed. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001.

Effects of the GLS inhibitor CB-839, alone or in combination with the glycolytic inhibitor 3PO on hematologic parameters in vivo. (A) Experimental setup. Drug treatment started after 4 weeks of engraftment, n = 12 mice per group. (B) Body weight monitoring during the course of the study, as an indicator of toxicity. (C) Spleen weight of the mice at the end of the treatment. (D) Top: effects on blood counts measured at week 4 of the treatment and at week 6. Middle: VF;GFP chimerism of different cell types in peripheral blood, calculated by % of GFP+ cells in each population analyzed by flow cytometry. From left to right: erythrocytes (Ter119+), platelets (CD61+), neutrophils (CD11b+ Gr1+), B-cells (B220+), and T-cells (CD3+). Bottom: red blood cell (RBC) count, MCV, and mean corpuscular hemoglobin (MCH) of RBCs. The area colored in gray depicts the normal range expected for WT mice. The plots represent the mean ± SEM. 2-way ANOVA for panels B,D or 1-way ANOVA for panel C with multiple comparisons with the vehicle group (Fisher LSD test) were performed. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001.

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