The fact that limited expression of ETV6-RUNX1 during early hematopoietic development conferred only a low risk of developing B-ALL, and only after exposure to common pathogens (10% incidence), explains the low incidence of B-ALL in human preleukemic carriers, and further validates the accuracy of this model. Here, RUNX1 is linked to precursor B-cell acute lymphoblastic leukemia.