C/EBPβ Sustains the Oncogenic Program of AML Cells by Cooperating with MYB and Co-activator P300 in a Transcriptional Module

Transcription factor MYB is a key regulator of gene expression in hematopoietic cells and has emerged as a novel drug target for acute myeloid leukemia (AML). Studies aiming to identify potential MYB inhibitors have found that the natural compound helenalin acetate (HA) inhibits viability and induces cell death and differentiation of AML cells by disrupting the MYB-induced gene expression program. Interestingly, CCAAT-box/enhancer binding protein β (C/EBPβ), a transcription factor known to cooperate with MYB and the co-activator p300 in myeloid cells, rather than MYB itself, was identified as the primary target of HA. This supports a model in which MYB, C/EBPβ, and p300 form the core of a transcriptional module that is essential for maintenance of the proliferative potential of AML cells, highlighting a novel role for C/EBPβ as a proleukemogenic factor.