These changes in immune cell types that do not express BTK could be due to a combination of direct effects via ibrutinib’s promiscuous inhibition of kinases other than BTK (including BLK, BMX, ITK, TEC, TXK, and EGFR43) and indirect effects arising from the ibrutinib-induced relocation of CLL cells from the protective microenvironment into the peripheral blood. This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.