To understand the mechanism of intrinsic sensitivity and resistance to I-BET, we have undertaken an integrative epigenomic, chemo-genomic and transcriptomic approach by assessing the effects of increasing concentrations of I-BET151 on chromatin-bound BRD2, BRD3 and BRD4 and gene expression in one resistant (K562) and one sensitive (MV4;11) leukemia cell lines. Here, BRD4 is linked to leukemia.