The most represented signatures during treatment revealed increase in signaling pathways such as apoptosis, transcriptional deregulation and inflammation, and a decrease in VEGF signaling and DNA replication, which is in line with the chromatin accessibility results obtained in CLL patients49, and likely due to ibrutinib-mediated suppression of proliferation and induction of apoptosis. This evidence concerns the gene VEGFA and B-cell chronic lymphocytic leukemia.