Hypoxic states reverse the effects of Meis1 depletion. (A) Quantitative real-time PCR analysis of a subset of Hif1α target genes in control and Meis1f/f MLL-AF9 cells treated with vehicle (Veh) or 4-OHT. The bar graph displays mean ± SEM. (B) Bar graph depicting colony numbers formed by Meis1f/f MLL-AF9 knockin cells under ambient air or hypoxia, treated with vehicle or 4-OHT. (C) MV4;11 cells transduced with control (NT) or MEIS1-shRNA were cultured in the presence of ambient air or hypoxia (3% oxygen). The bar graph depicts percentage (%) increase in growth over 72 hours for each condition. Data represent mean ± SEM of 2 independent experiments. *P < .01. (D) Meis1f/f MLL-AF9 leukemic cells were transduced with lentivirus-bearing control (NT) or Vhl-shRNA. Transduced cells were transplanted into irradiated mice and recipient animals treated with tamoxifen or vehicle as described. The graph depicts leukemia-free survival of the various groups of mice. *P < .01, log-rank test, n = 5 per group. (E) Fluorescence-activated cell sorting analysis of intracellular ROS (staining) in Meis1f/f MLL-AF9 knockin cells transduced with control (NT) or Vhl-shRNA and treated with vehicle or 4-OHT. Results of 1 representative experiment are shown (n = 3).