BCR::ABL1-induced enhancer reprogramming uncovers hypersensitivity of Ph+B-ALL cells to enhancer-targeting drugs [ChIP-Seq]

To better understand how BCR::ABL1 establishes the Ph+B-ALL-defining transcriptional program, we adopted an integrative multi-omics approach to study the transcriptome, enhancer activities, and 3-dimensional interactions of enhancers with target genes in Ph+B-ALL cells. We performed an in-depth analysis of cells from human Ph+B-ALL patients and a murine Ph+B-ALL model using ChIP-Seq, RNA-Seq, and Hi-C-based methods to link enhancers to the promoters they regulate. We further interfered with enhancer function to explore their role in Ph+B-ALL and investigated BCR::ABL1-regulated TFs that are recruited to them using targeted proteasomal degradation and RNA interference (RNAi).