Effects of the GLS inhibitor CB-839, alone or in combination with ruxolitinib in vivo. (A) Experimental setup. VF;GFP BM cells were transplanted in competition with WT cells at a 1 to 20 ratio and the treatment started 6 weeks after engraftment. N = 12 mice per group. (B) Body weight of the mice monitored during the treatment. (C) Spleen weight of the mice from each group at the end of the experiment (after 11 weeks of treatment). (D) Treatment-induced changes in blood glucose levels measured in nonfasting conditions. (E) Glucose tolerance test performed 10 weeks after starting the treatment (right), in which fasting mice for 8 hours were injected with glucose IP and blood glucose levels monitored at different time points. (F) Effects of the treatment on hemoglobin, platelet, and neutrophil count (top) and on VF; GFP chimerism (represented as percentage of GFP+ cells) in erythrocytes (Ter119+), platelets (CD61+), and neutrophils (Gr1+ CD11b+) (bottom). The area colored in gray depicts the normal range expected for WT mice. The plots represent the mean ± SEM. 2-way ANOVA was performed in panels B,D-F and 1-way ANOVA in panel C; followed by Fisher least significant difference (LSD) test. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001.