RUNX1 and leukemia: This model suggests that the pathogenesis of leukemia is caused by the double hits to the cell: one hit involves mutations of differentiation-associated genes such as RUNX1 and Etv1 (Grimwade et al., 2016; Zhao et al., 2014), which leads to aborted differentiation and accumulation of mutant cells; and the other hit involves mutations of proliferation-associated genes, such as Flt and Kit (Gilliland and Griffin, 2002), inducing the transformation of mutated cells into rapidly proliferating cells.