These active histone marks were reduced following pharmacologic inhibition of BRD4, along with reduced PRMT5 mRNA and protein expression in IGHV-U CLL cells (Supplemental Fig. 7C), suggesting PRMT5 may be regulated by BRD4-mediated priming of this enhancer and providing an additional therapeutically targetable mechanism for RT patients and for CLL at high risk of progression to RT alone or in combination with PRMT5i. Here, BRD4 is linked to B-cell chronic lymphocytic leukemia.