JQ1 treatment in vivo reduces c-Myc expression and significantly prolongs survival. (A) Experimental design. Tal1/Lmo2 mouse T-ALLs were transplanted (cell dose 10⁵) into syngeneic recipients and vehicle or JQ1 was administered at 50 mg/kg daily starting at the time of transplant and continuing for 3 consecutive weeks. Mice were monitored for disease and euthanized when they became moribund. (B) Survival was estimated using the Kaplan-Meier method and the difference in overall survival between the 2 groups assessed by the log-rank test. (C) c-Myc inhibition targets the LIC in Tal1/Lmo2 T-ALLs. Leukemic cells were diluted and transplanted into syngeneic mice. JQ1 was administered at 50 mg/kg daily starting at the time of transplant and continuing for 3 consecutive weeks. A log-log plot and LIC frequency was calculated using ELDA software for vehicle, (red, 1/17 970) and JQ1 (black, 1/199 871). A fraction of secondary recipients develop leukemia when transplanted with limiting dilutions of leukemic cells and treated with either vehicle or JQ1. (D) Leukemic mice remain responsive to JQ1 treatment. When disease was evident, a single dose of JQ1 was readministered and RNA isolated from mouse leukemic tissues. c-Myc expression was analyzed by quantitative real-time PCR. Copy number was normalized to β-actin using the ΔΔCT method. Each bar represents a single mouse and error bars represent SEM. **P < .01, ***P < .001, ****P < .0001.