In this study, we provide evidence that repression of C/EBPβ/JMJD3 partnership probably represents an essential oncogenic event for the maintenance of leukemic malignancy in certain subtypes of AML (mostly M2 and M3), and their overexpression drives these AML cells to undergo myeloid differentiation and lose their capacity to re-establish leukemia in vivo. Here, CEBPB is linked to leukemia.