Figure 3
Figure 3. Extrinsic apoptotic pathway is dispensable for therapeutic response of panobinostat. (A) Quantitative real-time PCR of Dr5 messenger RNA (mRNA) levels in spleen cells (>80% GFP-positive cells) isolated from A/E9a;NrasG12D leukemia recipient mice treated with panobinostat (25 mg/kg) or vehicle (D5W) for 4 hours. Mean value of 2 individual samples is shown. (B-C) Flow cytometry analysis of leukemic cells in peripheral blood and BLI of A/E9a;NrasG12D/DR5−/− leukemia recipient mice treated with panobinostat or vehicle using the standard therapy regimen. In panel B, each data point represents an individual mouse, and horizontal bars represent mean value. ***P < .0001. (D) Kaplan-Meier survival curves of treated A/E9a;NrasG12D/DR5−/− leukemia recipient mice following initiation of therapy (n = 10 for vehicle, n = 10 for panobinostat; median survival benefit 45 days, P < .0001). Dotted line represents final day of treatment.

Extrinsic apoptotic pathway is dispensable for therapeutic response of panobinostat. (A) Quantitative real-time PCR of Dr5 messenger RNA (mRNA) levels in spleen cells (>80% GFP-positive cells) isolated from A/E9a;NrasG12D leukemia recipient mice treated with panobinostat (25 mg/kg) or vehicle (D5W) for 4 hours. Mean value of 2 individual samples is shown. (B-C) Flow cytometry analysis of leukemic cells in peripheral blood and BLI of A/E9a;NrasG12D/DR5−/− leukemia recipient mice treated with panobinostat or vehicle using the standard therapy regimen. In panel B, each data point represents an individual mouse, and horizontal bars represent mean value. ***P < .0001. (D) Kaplan-Meier survival curves of treated A/E9a;NrasG12D/DR5−/− leukemia recipient mice following initiation of therapy (n = 10 for vehicle, n = 10 for panobinostat; median survival benefit 45 days, P < .0001). Dotted line represents final day of treatment.

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