The Essential Transcriptional Function of BRD4 in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is often initiated by genetic alterations of machineries that regulate chromatin and transcription, thereby blocking cell differentiation. Such mechanisms may also render leukemia cells vulnerable to perturbations of transcriptional regulators, which includes small molecules targeting the coactivator protein BRD4. Numerous studies have validated BRD4 as a therapeutic target in diverse subtypes of AML; however, the vital function of BRD4 in this disease is only beginning to be understood. Here we discuss the recent progress in elucidating the transcriptional function of BRD4 in AML cells, with an emphasis on the desirable attributes, but also the inherent limitations, of targeting general coactivator proteins as cancer therapy.