When we performed parallel enrichment analysis for transcription factors and their putative binding sites (Fig. 2e), we observed concerted changes for key regulators of B cell development such as BCL11A, EBF1, IKZF1, IRF4, MEF2A, NFATC1, PAX5, and POU2F2, indicating that BTK inhibition may trigger loss of B cell identity in CLL cells. Here, IRF4 is linked to B-cell chronic lymphocytic leukemia.