Studies of methyltransferase mutant, AF9-binding disrupted mutant, and wild type DOT1L models in vivo showed loss of DOT1L-AF9 was sufficient to inhibit leukemia cell growth and increase their differentiation to similar levels observed with DOT1L enzyme-dead mutant (Shen et al., 2013; Kuntimaddi et al., 2015; Grigsby et al., 2021). Here, MLLT3 is linked to leukemia.