In another trial focusing on CLL patients undergoing ibrutinib therapy with immunophenotyping, ATAC-seq, and scRNA-seq [121], robust reduced NF-κB binding activity was first observed after ibrutinib induction, followed by decreased regulatory activity of transcription factors involved in B cell development (e.g. EBF1, FOXM1, IRF4, PAX5, PU.1) and loss of B-cell surface markers in CLL cells (e.g. CD5 and CD19). This evidence concerns the gene IRF4 and B-cell chronic lymphocytic leukemia.