Figure 5.

Bromodomain and extraterminal domain inhibitors have the potential to reverse molecular changes caused by the ETV6 translocation. (A) A heatmap represents the relative expression levels of genes following 1μM JQ1 treatment for 24 hours (hr). Fold change of gene expression under treatment conditions over the control (DMSO) is shown. Exemplary genes are annotated. Each row corresponds to a gene. (B) Volcano plot showing up-regulated (right) or down-regulated (left) following 1μM JQ1 treatment for 24 hr compared with DMSO. (C) Gene Set Enrichment Analysis of DMSO (left) and JQ1 treatment (right). The differentially expressed genes of 2 groups were ranked according to their log10 (P value). (D) Downregulation of I L-3 RNA level by JQ1. ETV6::ACSL6 acute lymphoblastic leukemia (ALL) cells (2x10⁶ cells) were treated with JQ1 in a time and concentration dependent manner. (E) IL-3 concentration in the cell culture supernatant following 1μM JQ1 treatment for 24 hr. RJ-9: an ETV6::ACSL6 ALL patient; RJ-13: an ETV6::RUNX1 ALL patient. (F) BRD4 occupancy at the ETV6 gene locus in JQ1 and DMSO treated samples as determined by CUT&Tag. (G) BRD4 enrichment at the ETV6 locus as determined by CUT&Tag after DMSO (left) or 1μM JQ1 treatment for 24 hr. y axis shows BRD4 CUT&Tag signal in units of rpm/bp. (H) Genome-wide BRD4 binding level after 1 μM JQ1 treatment for 24 hr as identified by CUT&Tag. (I) Distribution of genomic elements associated BRD4 peaks following JQ1 treatment. Ctrl: control; BETi: bromodomain and extraterminal domain inhibitors.