RUNX1 and leukemia: RUNX1 mutations in leukemia are thought to play a role in differentiation dysregulation in this “2-hit” model (Conway O’Brien and Steven, 2014; Grimwade et al., 2016), albeit removing dysregulated wild-type RUNX1 in leukemia cells also causes a drastic reduction in cell numbers [Figure 2C, (Li et al., 2019; Sun et al., 2019)].