For instance, ibrutinib not only inhibits the secretion of cytokines, such as CCL3, CCL4, CXCL12, and CXCL13, from CLL cells and their supporting cells within the microenvironment, it also inhibits the TLR signaling pathway (38, 41), which prevents the homing and residence of CLL cells and dissociates these cells from the protective microenvironment (31, 41, 42). This evidence concerns the gene CCL4 and B-cell chronic lymphocytic leukemia.