An intriguing aspect of the clinical efficacy of BCR-signaling inhibitors such as ibrutinib is that they affect chemokine and integrin signaling leading to a redistribution of CLL cells from the lymph nodes into the peripheral blood.23,39,40 Therefore, while drugs such as ibrutinib metabolically reprogram CLL cells directly by inhibiting BCR-signaling, the movement of CLL cells out of the lymph nodes will also inhibit glycolysis by reducing interactions with stromal cells and exposure to hypoxia in the CLL nodal microenvironment. Here, BCR is linked to B-cell chronic lymphocytic leukemia.