This model also explains the distinct requirements of CBP and P300 in normal hematopoiesis and leukemia cell development (Cheng et al., 2017; Wang et al., 2011), as also observed in our studies in genetically diverse AML cell types, as well as the functional requirement for P300 in CBP-deficient cancers (Ogiwara et al., 2016). Here, EP300 is linked to acute myeloid leukemia.