Figure 8. Short-term in vivo administration of PI-103 combined with imatinib suppresses leukemic cell expansion more effectively than imatinib alone.

(A) Lethally irradiated syngeneic recipients were transplanted with p190 L-CFCs (hCD4⁺) together with normal BM, then treated on days 11–13 after injection (i.p.; 2 days of treatment) with single and combination doses of imatinib (70 mg/kg, b.i.d.) and rapamycin (7 mg/kg, once per day) or imatinib and PI-103 (40 mg/kg, b.i.d.) or double placebo control (diH₂O and 75%/25% DMSO/saline mixture, b.i.d.) prior to sacrifice. Spleen weights after treatment regimen are reported. (B) Percent apoptosis in the BM and spleen was determined by annexin V/7AAD staining of hCD4⁺ blasts after 2-day treatment regimen. (C) Two hours prior to sacrifice, mice were injected with 5-ethynyl-2′-deoxyridine (EdU; i.p., 1.125 mg) and assayed for cycling cells that incorporated EdU in the BM and spleen with Click-iT EdU AF647 azide and propidium iodide staining (left and right panels). Representative depiction of cycling cells in the BM (left panel). *P < 0.05, ^‡P < 0.01, **P < 0.001 versus control; ^#P < 0.05, ^†P < 0.01 versus imatinib; 1-way ANOVA; mean values ± SEM are shown; n = 5 mice per treatment group.