Comparison of responsiveness to ABT-737 and ABT-199. (A-B) WBC counts, (C-D) platelet counts, and (E-F) Kaplan-Meier survival curves of mice transplanted with 4 bim^+/+ (nos. 9, 12, 16, and 47) and 3 bim^−/− (nos. 58, 96, and 324) myc/bcl-2 lymphomas and treated with ABT-737, ABT-199, or the respective vehicles (3 mice per treatment arm for each independent tumor). Blood analyses were performed at 0 hours, 3 hours, and 6 days after starting treatment (day 11 after transplantation), using an ADVIA 2120 hematology analyzer (Siemens Australia New Zealand, VIC, Australia). Bars represent mean + SEM; significant changes observed at 3 hours are indicated: *P < .05, **P < .01, ***P < .001, Student t test. The x-axis in panels E and F indicates days elapsed since start of treatment; the bar indicates the duration of treatment (10 days). Significance for Kaplan-Meier survival curves was determined using the log-rank (Mantel-Cox) test. The median survival of bim^+/+ lymphomas treated with ABT-737 was 21.5 days vs 14 days for vehicle (P = .0088), and 23.5 days with ABT-199 vs 13 days for vehicle (P = .0003). The median survival of bim^−/− lymphomas treated with ABT-737 was 20.5 days vs 14 days for vehicle (P < .0001), and 19.5 days with ABT-199 vs 13 days for vehicle (P < .0001). One bim^−/− lymphoma (no. 324) rebounded early following treatment; unusually, it comprised 50% progenitor (B220⁺CD4⁺) and 50% B-lymphoid (B220⁺CD4⁻) cells, the latter having higher levels of Mcl-1 (see supplemental Figure 1A), which would confer greater resistance.