The BET inhibitor GNE-987 effectively induces anti-cancer effects byfocusing on super-enhancers inT-cell acute lymphoblastic leukemia [Cut & Tag]

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignant tumor that arises from T progenitor cells and accounts for 15% of childhood ALL and 25% of adult ALL cases. GNE-987 is a new chimeric molecule designed by proteolysis-targeting chimeras (PROTAC) technology. that combines an effective bromodomains and extra-targeting (BET) protein inhibitor with E3 ubiquitin ligase VHL(Von Hippel Lindau) and effectively induces proteasomal degradation of bromodomain-containing protein 4 (BRD4). GNE-987 and persistently inhibits cell proliferation and induces apoptosis, however, its anti-tumor activity GNE-987 in T-ALL has not been clarified, Here, we explore the molecular mechanisms underlying GNE-987's anti-tumor effect in T-ALL using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP seq) and Cut&Tag technology. Genome binding/occupancy profiling of Jurkat and 6T-CEM cells treated with 10 nM for 24 h were generated by CUT&Tag.