Indeed, mutated or de-regulated master transcription factors are regularly identified as oncogenic drivers in leukemia.[19–27] Mutations in the CEBPA gene are found in 10–15% of de novo acute myeloid leukemia (AML) cases, predominantly in patients with normal karyotype acute myeloid leukemia (NK-AML).[28–30] The mutations are not equally distributed across the CEBPA locus but cluster in two hotspots in different regions of the gene (Figure 1). This evidence concerns the gene CEBPA and acute myeloid leukemia.