Constitutive BCR signaling results in enhanced activity of kinases downstream of BCR, including phosphatidylinositol 3-kinase (PI3K) and Bruton tyrosine kinase (BTK), and drives not only the autonomous proliferation and survival of tumor cells, but also homing of tumor cells to protective niches in the BM and lymph nodes, providing the preclinical rationale for testing venetoclax in combination with PI3K and BTK inhibitors, which are known to mobilize CLL cells into the peripheral blood (PB) compartment. This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.