Figure 5.
Combined treatment with SLC-391 and venetoclax decreases leukemia burden and significantly enhances survival of leukemic mice in a PDX model. (A) Schematic overview of PDX study design. In cohort 1, 20 mice received cells from patient #2 (5 mice each were treated with vehicle, 50 mg/kg SLC-319 [SLC], 50 mg/kg venetoclax [VEN], or SLC+VEN combination therapy for 4 weeks). In cohort 2, 22 mice received cells from patient #14 (4 were treated with vehicle, 6 were treated with SLC, 5 were treated with VEN, and 7 were treated with SLC+VEN combination therapy for 4 weeks at the same drug concentrations used for cohort 1). (B) Representative bioluminescent imaging of mice from cohort 1 and quantification of results of mice from cohort 1 (1 and 3 weeks after oral gavages with the indicated drugs) and cohort 2 (1 week after oral gavages with the indicated drugs. The P values were calculated using 1-way ANOVA with Tukey's post hoc correction for multiple comparisons. (C) Spleen sizes and weights from representative euthanized mice from each treatment group for each patient cohort 3 weeks after oral gavages. (D) FACS analyses quantifying the percentages of transduced (GFP+) and untransduced (GFP−) engrafted human leukemic cells in PB and BM from 1 representative animal from each cohort and treatment group 3 weeks after oral gavage. (E) FACS analysis quantifying the percentages of transduced (GFP+) and untransduced (GFP−) engrafted CD34+CD38− human leukemic cells in the CD45+ BM compartment from 1 representative animal from each cohort and treatment group 3 weeks after oral gavages. (F) Kaplan-Meier survival curves of leukemic mice reaching the experimental end point in the indicated treatment groups for both cohorts (n = 4-7 mice per group). Median survival for each treatment group is indicated in days in parentheses. The P values were calculated using a log-rank (Mantel-Cox) test, and significant differences between groups are indicated. α-DT, antidiphtheria toxin; IP, intraperitoneal; IVIS, in vivo imaging system; Veh., vehicle.

Combined treatment with SLC-391 and venetoclax decreases leukemia burden and significantly enhances survival of leukemic mice in a PDX model. (A) Schematic overview of PDX study design. In cohort 1, 20 mice received cells from patient #2 (5 mice each were treated with vehicle, 50 mg/kg SLC-319 [SLC], 50 mg/kg venetoclax [VEN], or SLC+VEN combination therapy for 4 weeks). In cohort 2, 22 mice received cells from patient #14 (4 were treated with vehicle, 6 were treated with SLC, 5 were treated with VEN, and 7 were treated with SLC+VEN combination therapy for 4 weeks at the same drug concentrations used for cohort 1). (B) Representative bioluminescent imaging of mice from cohort 1 and quantification of results of mice from cohort 1 (1 and 3 weeks after oral gavages with the indicated drugs) and cohort 2 (1 week after oral gavages with the indicated drugs. The P values were calculated using 1-way ANOVA with Tukey's post hoc correction for multiple comparisons. (C) Spleen sizes and weights from representative euthanized mice from each treatment group for each patient cohort 3 weeks after oral gavages. (D) FACS analyses quantifying the percentages of transduced (GFP+) and untransduced (GFP−) engrafted human leukemic cells in PB and BM from 1 representative animal from each cohort and treatment group 3 weeks after oral gavage. (E) FACS analysis quantifying the percentages of transduced (GFP+) and untransduced (GFP−) engrafted CD34+CD38− human leukemic cells in the CD45+ BM compartment from 1 representative animal from each cohort and treatment group 3 weeks after oral gavages. (F) Kaplan-Meier survival curves of leukemic mice reaching the experimental end point in the indicated treatment groups for both cohorts (n = 4-7 mice per group). Median survival for each treatment group is indicated in days in parentheses. The P values were calculated using a log-rank (Mantel-Cox) test, and significant differences between groups are indicated. α-DT, antidiphtheria toxin; IP, intraperitoneal; IVIS, in vivo imaging system; Veh., vehicle.

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