Intrinsic apoptotic pathway is dispensable for therapeutic response to panobinostat. (A-B) Flow cytometry analysis of leukemic cells in peripheral blood and BLI of A/E9a;Nras^G12D/Bcl-2 leukemia recipient mice treated with panobinostat or vehicle using the standard therapy regimen. In panel A, each data point represents an individual mouse, and horizontal bars represent mean value. ***P < .0001. (C) Kaplan-Meier survival curves of treated A/E9a;Nras^G12D/Bcl-2 leukemia recipient mice following initiation of therapy (n = 12 for vehicle, n = 8 for panobinostat; median survival benefit 63 days, P < .0001). Dotted line represents final day of treatment. (D) Analysis of apoptotic cells via TUNEL staining. Staining was performed on bone marrow isolated from A/E9a;Nras^G12D leukemia recipient mice treated with panobinostat (25 mg/kg) or cytarabine (100 mg/kg) for the indicated time. Sections are representative of 3 (panobinostat) or 2 (cytarabine) mice per time point. Dark brown cells indicate TUNEL-positive cells. (E) Flow cytometry analysis of GFP-positive leukemic cells in indicated tissue isolated from A/E9a;Nras^G12D leukemia recipient mice treated with panobinostat (25 mg/kg) or vehicle (D5W, 250 µL) for 3 days. Data are combined from 2 individual experiments. Each data point represents an individual mouse, and horizontal bars represent mean value. **P = .004 (blood); **P = .0022 and P = .0012, respectively (spleen); ***P < .0001 (bone marrow).