In addition to DOT1L’s methyltransferase activity, studies have shown that loss of Dot1 complex (DotCom, composed of AF9, AF10, ENL and AF17) components AF10 (Deshpande et al., 2014), and ENL (Wan et al., 2017) have a similar effect on leukemia cells as loss of DOT1L. Here, MLLT1 is linked to leukemia.