In the present work, we sought to overcome this limitation by comparing CEBPA-mutant AML in the presence and absence of additional mutations in TET2. By combining transcriptomic and epigenomic analyses of relevant in vitro and in vivo models as well as data from AML patients, we identified an intricate mechanism where TET2 loss-of-function rebalances Gata2 expression levels in CebpaDM AML, and hence drives an aggressive disease. Here, CEBPA is linked to acute myeloid leukemia.