These signals are likely relevant in patients because TLR9 and IL15R are expressed by CLL-cells [47–49]; TLR9 signaling is a strong activator of AKT and ERK in CLL cells [41] and of BTK in normal B cells [42]; and IL15, which is constitutively produced by stromal cells in bone marrow, spleen, and LN [50–52], promotes the growth of leukemic B cells [49, 50]. Here, BTK is linked to B-cell chronic lymphocytic leukemia.