CP-690,550 showed therapeutic efficacy in a mouse model of B1 IL-15–transgenic CD8 T-cell leukemia that manifested an autocrine IL-15/IL-15Rα loop that acts through Jak3/STAT5. (A) Serum levels of human IL-15 from the human IL-15–transgenic CD8 T-cell leukemia–bearing mice after inoculation of tumor cells. (B) Serum levels of mouse IL-15Rα from the IL-15–transgenic CD8 T-cell leukemia–bearing mice after inoculation of tumor cells. (C) Kaplan-Meier analysis demonstrating CP-690,550 prolongation of the survival of mice bearing the IL-15–transgenic CD8 T-cell leukemia. Mice in the control group received PEG300 by subcutaneous pump for 14 days. Mice in the CP-690,550-pre group (CP-pre) received a pump infusion with CP-690,550 at 30 mg/kg/d for 14 days that was placed into the mice 2 days before tumor cell inoculation. Mice in the CP-690,550-post group (CP-post) received a pump infusion with CP-690,550 at 30 mg/kg/d for 14 days that was placed into the mice 1 day after inoculation of the leukemic cells. Mice in the anti–human IL-15 monoclonal antibody M111 group received M111 at 100 μg intraperitoneally weekly for 2 weeks starting at 3 days after inoculation of the leukemic cells. (D) CP-690,550 inhibited the phosphorylation status of Jak3/STAT5 in splenocytes from IL-15–transgenic CD8 T-cell leukemia–bearing mice. Mice in the tumor-only group received PEG300 by a subcutaneous pump for 14 days. Mice in the CP-690,550 group (CP) received a pump infusion with CP-690,550 at 30 mg/kg/d for 14 days that was placed into the mice 1 day after inoculation of the leukemic cells. Mice in the M111 group received M111 at 100 μg intraperitoneally weekly for 2 weeks starting at 3 days after inoculation of the leukemic cells. Mice in the normal group (no tumor, no treatment) were used as a control. The splenic cells were separated 13 days after tumor cell inoculation and checked for the phosphorylation status of STAT5. *P < .00001.