BEZ235 induces apoptotic regressions and prolongs survival in Eμ-Myc lymphoma. Cohorts of mice (n = 9 per treatment condition) were injected intravenously with Eμ-Myc cells and allowed to develop disseminated lymphoma prior to initiation of daily treatment with BEZ235 (50 mg/kg by mouth) or vehicle (0.5% methylcellulose [MC]). (A) Peripheral white blood cell (WBC) counts for BEZ235 and vehicle-treated mice. (B) Subgroups of mice (n = 3 per treatment group) were monitored by ¹⁸F-FDG-PET scanning, with PET avidity quantified as a tumor:background ratio for axillary and inguinal lymph nodes. (C) Lymph node apoptosis was assessed by using fluorescent-activated cell sorting for sub G1 fraction on nuclear PI staining for cell suspensions prepared from 3 individual mice per treatment group at each time point. (D) Lymph nodes collected from mice on day 4 of treatment were harvested for protein lysates, separated by SDS-PAGE, and probed for phosphorylated proteins as indicated in figure legends. Lysate obtained from an untreated lymphoma transduced with a constitutively activated (myristoylated [MYR]) AKT is provided as a control. Each lane represents a lymph node lysate from an individual mouse. (E) Lymph nodes obtained from mice on day 4 of treatment with BEZ235 or vehicle were immunoblotted for BMF expression. Each lane represents a lymph node lysate from an individual mouse. (F) Kaplan-Meier survival curves for cohorts of mice (n = 10 per treatment condition) bearing p53-null (#3239) lymphoma and treated daily with BEZ235 or vehicle from day 3 after receiving transplanted cells (period of dosing indicated in gray). (G) Survival curves for cohorts of mice (n = 10 per treatment condition) bearing p53-competent (#102) lymphoma treated daily with BEZ235 from day 3 after receiving transplanted cells. In each case, a statistically significant prolongation of survival was observed (log-rank P < .05,). *P < .05 (Student t test).