Figure 5
Figure 5. Eμ-myc lymphomas forced to overexpress Bcl-2 throughout lymphomagenesis are hypersensitive to ABT-737. (A) Myc-positive fetal liver progenitor cells were transduced with MSCV, MSCV-Bcl-2, MSCV-Bcl-w, and MSCV-Mcl-1 retrovirus and injected into irradiated recipient PTPRCA mice (MSCV [n=54[,MSCV-Bcl-2 [n=18[, MSCV-Bcl-w [n=8[, and MSCVMcl-1 [n=8[). GFP-positive cells were injected into irradiated recipient PTPRCA mice (MSCV [n = 54], MSCV-Bcl-2 [n = 18], MSCV-Bcl-w [n = 8], and MSCV-Mcl-1 [n = 8]). Lymphomagenesis was monitored and Kaplan-Meier survival curves were obtained. Lymphoma cells harvested from the mice at sacrifice, designated FLR-Eμ-myc lymphomas, were stored for further use. (B) Western blot was performed using whole cell lysates from representative FLR-Eμ-myc/Bcl-2 and FLR-Eμ-myc/Mcl-1 cells (both derived from pool no. 12 of fetal liver cells) and antibodies against Mcl-1, Bcl-2, and α-tubulin. (C) FLR-Eμ-myc/Bcl-2 (top panels) and FLR-Eμ-myc/Mcl-1 cells (bottom panels) were treated with increasing concentrations of ABT-737 or ABT-737e. Cell membrane disruption (left panels) and MOMP (right panels) were assessed by PI and TMRE staining, respectively. Results shown are the mean and SE from at least 3 separate experiments. (D) The cell-cycle profile of FL-Eμ-myc/Bcl-2 cells cultured ex vivo was obtained by analyzing the DNA content of cells by fluorescence-activated cell sorting (FACS) after incubation in a hypotonic solution containing PI.

Eμ-myc lymphomas forced to overexpress Bcl-2 throughout lymphomagenesis are hypersensitive to ABT-737. (A) Myc-positive fetal liver progenitor cells were transduced with MSCV, MSCV-Bcl-2, MSCV-Bcl-w, and MSCV-Mcl-1 retrovirus and injected into irradiated recipient PTPRCA mice (MSCV [n=54[,MSCV-Bcl-2 [n=18[, MSCV-Bcl-w [n=8[, and MSCVMcl-1 [n=8[). GFP-positive cells were injected into irradiated recipient PTPRCA mice (MSCV [n = 54], MSCV-Bcl-2 [n = 18], MSCV-Bcl-w [n = 8], and MSCV-Mcl-1 [n = 8]). Lymphomagenesis was monitored and Kaplan-Meier survival curves were obtained. Lymphoma cells harvested from the mice at sacrifice, designated FLR-Eμ-myc lymphomas, were stored for further use. (B) Western blot was performed using whole cell lysates from representative FLR-Eμ-myc/Bcl-2 and FLR-Eμ-myc/Mcl-1 cells (both derived from pool no. 12 of fetal liver cells) and antibodies against Mcl-1, Bcl-2, and α-tubulin. (C) FLR-Eμ-myc/Bcl-2 (top panels) and FLR-Eμ-myc/Mcl-1 cells (bottom panels) were treated with increasing concentrations of ABT-737 or ABT-737e. Cell membrane disruption (left panels) and MOMP (right panels) were assessed by PI and TMRE staining, respectively. Results shown are the mean and SE from at least 3 separate experiments. (D) The cell-cycle profile of FL-Eμ-myc/Bcl-2 cells cultured ex vivo was obtained by analyzing the DNA content of cells by fluorescence-activated cell sorting (FACS) after incubation in a hypotonic solution containing PI.

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