Dimerization-induced RUNX1/p300 phosphorylation cascade and its proposed central role in hematopoiesis and leukemia. A schematic that summarizes the findings reported in this study. The left panel illustrates the initiation of a phosphorylation cascade after the dimerization of RUNX1 with PEBP2-β at functional binding sites. This leads to the activation of specific target genes and enables RUNX1/PEBP2-β to act as master regulators of hematopoiesis. The right panel shows known leukemogenic genetic alterations in the components of this proposed cascade, indicating its central importance. The targeting of this phosphorylation cascade may represent a common mechanism in the genesis of RUNX1-related leukemia.