Abrogating MLL-ENL expression leads to elimination of established leukemias in vivo. (A) Effect of doxycycline on survival of recipient mice (left panel) and elimination of leukemic cells from peripheral blood (right panel). Recipient mice were transplanted with the indicated leukemic cells and after their detection in the peripheral blood, one group was given doxycycline in their water (◇: cME3a, n = 6; ME4a, n = 5; ME5a, n = 5; ME7c, n = 4) and the other left untreated (●: cME3a, n = 4; ME4a, n = 5; ME5a, n = 5; ME7c, n = 5). Arrows represent the point at which doxycycline treatment started; bars on the survival curves represent the length of treatment in each experiment. Doxycycline-treated mice are still alive 350, 270, and 360 days after transplantation of ME4a, ME5a, and ME7c cells, respectively. The graphs depict the presence of leukemic cells (Mac1⁺CD45.2⁺ cells in CD45.1 recipient mice for cME3a, and Mac1⁺EGFP⁺ cells for ME4a, ME5a, and ME7a) as a percentage of total Mac1⁺ cells in the peripheral blood of recipient mice. Points on the graphs represent mean values; bars represent SD. (B) The presence of Mac1⁺EGFP⁺ leukemic ME4a cells in the peripheral blood of recipient mice before (day −1) and after (day 6 and 34) their treatment (right panel), or not (left panel), with doxycycline. Numbers in the top right quadrant represent Mac1⁺EGFP⁺ cells as a percentage of total Mac1⁺ cells. No mice in the untreated group survived until the last time point shown, indicated by NS.