Figure 7.

Concurrent all-trans retinoic acid (ATRA)/bexarotene treatment reduces MLL-AF9 leukemia burden in vivo. (A) Schema for leukemia transplant procedure and in vivo treatment. Sublethally irradiated FVB mice were transplanted with 0.5x106 MLL-AF9 leukemia cells. Ten days later the mice were divided in four different cohorts and treated with 21-day release ATRA pellets. 5 mg: n=5 (~0.23 mg/day), 10 mg: n=5 (~0.5 mg/day), and 25 mg: n=8 (~1.2 mg/day). One day after pellet implantation, bexarotene (50 mg/kg) was delivered by oral gavage as indicated. A control cohort was implanted with placebo pellets and treated with the vehicle gavage (n=12). IV: intravenous. (B) The mice were sacrificed 21 days from pellet implantation and the spleen weight analyzed. (C) Kaplan-Meier survival curve analysis of mice transplanted with MLL-AF9 cells and treated as indicated in (A). (D) Schema for leukemia transplant procedure and mice treatment. FVB mice were transplanted with 1.5x106 MLL-AF9 leukemia cells by intraperitoneal (IP) injection. Five days later the mice were divided in four different cohorts and implanted with 21- day release ATRA pellets 25 mg (~1.2 mg/day) or placebo pellets. One day after pellet implantation, bexarotene (Targretin, 50 mg/kg) was delivered by oral gavage as indicated. (E) Kaplan-Meier survival curve analysis of mice transplanted with MLL-AF9 cells and treated as indicated in (E). *P<0.05, **P<0.01, ***P<0.001, t-test.