TKIs induce peripheral lymphocytosis at the start of therapy because of the redistribution of leukemic cells from lymphoid compartments to the circulation, due to many effects, including the inhibition of BcR signaling induced by exogenous or self-antigens, of autonomous signaling and of signaling from other surface structures, such as CXCR4, that contribute to the retaining of CLL cells in tissues. This evidence concerns the gene CXCR4 and B-cell chronic lymphocytic leukemia.