DOT1L and leukemia: Hence, the ectopic enzymatic activity of DOT1 L is thought to be leukaemogenic in MLL-r leukaemia, an inference that is supported by preclinical studies of DOT1 L knockdown with shRNA [13] or inhibition by small molecule inhibitors [14,15] and by the clinical activity of the DOT1 L inhibitor pinometostat in MLL-r leukaemia patients (vide infra) [16].