amp;Run assay, an alternative to ChIPseq, in the MEC1 cell line, to characterize genes directly regulated by this transcription factor. Apart from the regulation of the BCR signaling pathway, we noticed its potential in response to other drugs such as the BH3 mimetic (BCL2 inhibitor) venetoclax that has been recently approved for CLL therapy. Altogether, we thoroughly describe particular changes in CLL transcriptome, that provide increase in survival of leukemic cells during the BCR inhibitors therapy in both primary CLL cells and cell lines. Based on these results, we further suggest a rational combinatorial treatment of ibrutinib/idelalisib with an inhibitor targeting the transcription factor as a potential therapeutic strategy to eliminate mechanism of adaptation to BCR inhibitors.