Loss of Meis1 impedes propagation of MLL-fusion gene leukemia. Retroviral and knockin models of leukemia were generated as described. (A) Colony-replating assays were performed in methylcellulose media supplemented with 4-OHT or vehicle. Bar graphs represent colony numbers from 1 representative experiment for each leukemia model. Data represent mean ± standard error of the mean (SEM) of triplicates. *P < .01, Student t test. (B) Genomic PCR and Western blot demonstrating Meis1 depletion by 4-OHT treatment in Meis1f/f MLL-AF9 knockin cells. (C) Meis1f/f MLL-AF9 cells were transduced with control (MSCV) or Meis1 retrovirus. The bar graph represents colony numbers formed by transduced cells cultured in the presence of vehicle or 4-OHT. Data are mean ± SEM for 3 independent experiments. (D) MV4;11, THP-1, CBMA9.3NRas, and Kasumi-1 cells were transduced with lentivirus carrying shRNA against Meis1 or nontargeting (NT) control. Transduced cells were cultured in liquid medium. Cell growth was assessed by counting viable cells, at designated days post-puromycin selection. (E) Leukemic blasts from patients were transduced with MEIS1- or NT-shRNA. Line graphs depict growth curves of 3 different patient samples. (F) Control or Meis1f/f MLL-AF9–transformed cells (retroviral and knockin) were transplanted into irradiated mice. Animals were treated with tamoxifen or vehicle. Graphs depict leukemia-free survival of the various groups in the retroviral (left) and knockin (middle) or Meis1-overexpressed knockin (right) models. n = 5 to 10 mice per group. *P < .01, log-rank test.