Lymphoma characterization, B-cell isolation, and therapy of double Eμ-Myc- and BIM-deficient transgenic mice. (A) Kaplan-Meier survival curves for Eμ-MYC and Eμ-Myc-BIM^+/− mice. (B) Determination of BIM protein expression levels in B220⁺IgM⁺ mature Eμ-MYC and Eμ-Myc-BIM^+/− lymphomas by Western blot analysis. (C) Mature B220⁺IgM⁺ tumor lymphocytes isolated from Eμ-MYC and Eμ-Myc-BIM^+/− mice were BCR-activated with anti-IgM and treated with doxorubicin. Eμ-Myc B220⁺IgM⁺ lymphoma cells showed decreased survival and higher apoptotic levels than Eμ-Myc-BIM^+/− B220⁺IgM⁺ lymphoma cells, according to annexin V/fluorescein isothiocyanate staining. (D) Representative diagram of the experimental therapeutic design to test whether Eμ-MYC lymphoma cells were more sensitive than Eμ-MYC-BIM^+/− lymphoma cells to doxorubicin treatment in vivo. (E) Kaplan-Meier survival curves for mice transplanted with mature B-cell Eμ-Myc and Eμ-Myc-BIM^+/− lymphoma cells treated with doxorubicin versus vehicle. Compared with DMSO-treated mouse recipients, mice carrying Eμ-Myc lymphomas presented longer survival after therapy than those with Eμ-Myc-BIM^+/− lymphomas. (F) Micro-PET studies showed a significant reduction in the glycolytic tumor activity in Eμ-Myc lymphoma recipients compared with mice with Eμ-Myc-BIM^+/− lymphomas. PET studies were performed at day 7 (just before initiation of therapy) and at day 14 (1 week after therapy).