Strikingly, even within the Plag1/MLL-AF9 transplanted mice, we observed a marked expansion of the dual Plag1/MLL-AF9 (YFP+/mCherry+)–transduced cells over the single MLL-AF9 (YFP+ only)–expressing leukemia cells (from a 1:1 ratio at the time of transplant to an average of 12:1 at the time of necropsy; Fig. S5 d) when BM tissues were analyzed (Fig. 5 h), demonstrating a strong selective advantage for the combination of MLL-AF9 and Plag1. These data identify Plag1 as an oncogene whose de-repression contributes to EZH2-mutated AML. This evidence concerns the gene MLLT3 and leukemia.