Fig. 8
From: Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia
CEBPA mutations initiate AML through disruption of myeloid lineage enhancers. During normal myeloid differentiation, GCSF/CSF3R signaling drives both differentiation and proliferation of myeloid precursors. The differentiative program downstream of GCSF/CSF3R signaling is dependent on CEBPA acting at myeloid lineage enhancers. Mutant CEBPA blocks activation of these enhancers preventing transcription of differentiation-associated genes. When CSF3R mutations are introduced early, they activate transcription using the native enhancer repertoire initiating differentiation. Importantly this differentiation is insensitive to subsequent introduction of mutant CEBPA.
