The transcription factor NFATC1, which is a downstream effector of BCR signaling, is hypo-methylated and its expression levels along with expression levels of its target genes (BCL2, CCND1) have been can be directly correlated to CLL progression This hypo-methylation and expression of NFATC1 could be potentially blocked by ibrutinib in CLL treatment [172]. This evidence concerns the gene BCL2 and B-cell chronic lymphocytic leukemia.