Although the DOT1L methyltransferase inhibitor, pinometostat, has cell-inhibitory effect in cells and in vivo models of MLL-r leukemia (Daigle et al., 2013), recent results from a phase I clinical trial indicated that the small molecule has only modest efficacy in treating MLL-r leukemias (Stein et al., 2018). This evidence concerns the gene DOT1L and leukemia.