Meis1 knockdown induces cell-cycle arrest and apoptosis and delays establishment of leukemia in vivo. The 4166 cells were transduced with M26 or control virus as described and cultured for 48 hours without puromycin. (A) Top panel: Nuclei were extracted and stained with PI. Analysis of DNA content by flow cytometry showed an increase in the proportion of G0/G1 nuclei (left peak) in M26-transduced cells compared with control virus. Bottom panel: Increased apoptosis was evident by an increase in the uptake of PI and the pan-activated caspase maker CaspaTag. (B) Lethally irradiated mice were given 4166 cells that were either untreated or transduced with M26 or control virus as described. Mice were killed when showing signs of distress. The graph shows a survival analysis comparing the 3 groups (9 mice per group). Mice receiving M26-transduced cells had significantly prolonged survival (P < .001). (C) MEIS1 knockdown inhibits growth of human MLL-fusion gene leukemia cell lines. The cell lines indicated were transduced with MEIS1 shRNA lentivirus or control lentivirus for 3 to 5 days as described at MOI of 10 to 50. Bars represent relative cell growth and MEIS1 expression compared with controls (mean ± SE; n = 3; P < .05 except for HPB-NULL).
