Figure 1

A combination of the HDACi panobinostat and arsenic trioxide (ATO) demonstrates greater therapeutic efficacy against A/E9a;Nras -driven tumors. (A) Kaplan-Meier survival curves of mice bearing A/E9a;Nras ^G12D-driven leukemias treated with either vehicle (downward triangle), panobinostat (square), ATO (upward triangle) or a combination of panobinostat (pan) and ATO (circle). (n = 6 mice/group. Median survival benefit of panobinostat + ATO combination over panobinostat alone is 38.5 days; *P <0.05. and 95.5 days over vehicle alone; **P <0.001). Dotted lines indicate treatment days (5 days/ week; Monday through Fri) with the darker shaded area indicating the first week with a high dose of panobinostat (25 mg/kg) and the lighter shaded areas indicating the following three weeks with a lower dose of panobinostat (15 mg/kg). (B) Flow cytometry analysis of GFP-positive cells in the peripheral blood of mice treated for 5 days as indicated. (n = 3 to 6 mice per treatment group. Data are represented as the mean plus the standard error of the mean (SEM). *P <0.02).