TAT-NPMΔC delays leukemia development. (A) 106Fancc−/− preleukemic cells (along with 106 competitive cells) were injected intrvenously into lethally irradiated recipients, which after 10 days were injected intraperitonally with the indicated proteins (10 mg/kg in 0.5 mL PBS and 10% glycerol) twice a week for up to 12 weeks. Survival of recipient mice was quantified by Kaplan-Meier analysis. Experiments were performed 2 times, each with 3 recipient mice (total, 6 mice per group). (B) 2 × 105 WT BM cells or Fancc−/− leukemic cells were treated with BSA, TAT-NPM, or TAT-NPMΔC (30 μg/mL each) for 30 minutes. Cells were then washed and cultured for 24 hours in normal growth medium supplemented with 10 μM BrdU, and level of BrdU incorporation was determined by flow cytometry. Data represent mean plus or minus SD of 3 experiments. (C) TAT-NPMΔC inhibits leukemic cell proliferation. Tissue sections of spleen and liver from recipient mice treated with the indicated proteins for 4 weeks were stained with ki-67 and counterstained with hematoxylin and eosin (H&E). Magnification, 40×. (D) TAT-NPMΔC induces apoptosis in leukemic mice. Tissue sections of bone marrow from recipient mice treated with the indicated proteins for 4 weeks were analyzed by TUNEL staining (green). Magnification, 40×.
