As mentioned previously, CDK9 is a key protein in P-TEFb and is responsible for promoting the expression of several oncogenes, including c-Myc, when it is recruited by Brd4 (Fig. 5a).281 Supporting this, voruciclib is a second-generation CDK9 inhibitor that has been demonstrated to downregulate c-Myc in AML cell lines and primary patient samples (Fig. 5b).109 Interestingly, it also synergistically enhances the antileukemic activity of venetoclax through this mechanism (confirmed by c-Myc inhibition with 10058-F4) and the combination prolonged survival in AML xenograft models. This evidence concerns the gene BRD4 and acute myeloid leukemia.