Figure 7.
Combinatorial use of BCL-XL inhibitors and cytarabine demonstrates greater reduction of leukemic burden in vivo than single-agent treatment. (A) Dose-response curves and IC50 values (supplemental Table 13) determined for all 6 samples of CG2 AMKL, submitted to a viability assay in presence of cytarabine. (Cell-Titer Glo, 6-day incubation, 4 replicates). Viability readout was normalized to DMSO controls for each sample. (B) Schematic overview of experimental design of combinatory treatments with navitoclax and cytarabine (AraC) of mice that received xenotransplantation. (C) Percentage of leukemic blasts in the peripheral blood (% GFP+hCD45+, left graph), infiltration of the BM (middle graph) and spleen (right graph) was assessed in mice that received transplantation, after 3 weeks of indicated treatments. (D) Percentage infiltration (% GFP+hCD45+) in the BM of mice that received xenotransplantation and that were treated was compared at the end point between matched Vehicle controls and mice either treated with DT2216 or navitoclax (Navito) (E) as well as their respective combinations with cytarabine (AraC).

Combinatorial use of BCL-XL inhibitors and cytarabine demonstrates greater reduction of leukemic burden in vivo than single-agent treatment. (A) Dose-response curves and IC50 values (supplemental Table 13) determined for all 6 samples of CG2 AMKL, submitted to a viability assay in presence of cytarabine. (Cell-Titer Glo, 6-day incubation, 4 replicates). Viability readout was normalized to DMSO controls for each sample. (B) Schematic overview of experimental design of combinatory treatments with navitoclax and cytarabine (AraC) of mice that received xenotransplantation. (C) Percentage of leukemic blasts in the peripheral blood (% GFP+hCD45+, left graph), infiltration of the BM (middle graph) and spleen (right graph) was assessed in mice that received transplantation, after 3 weeks of indicated treatments. (D) Percentage infiltration (% GFP+hCD45+) in the BM of mice that received xenotransplantation and that were treated was compared at the end point between matched Vehicle controls and mice either treated with DT2216 or navitoclax (Navito) (E) as well as their respective combinations with cytarabine (AraC).

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