Recent studies from the Lerner laboratory showed that rolipram induced apoptosis of both IGHV unmutated and mutated CLL cells, suggesting that cAMP signaling may abrogate a TLR9-mediated survival signal in prognostically unfavorable IGHV unmutated CLL cells, and indicating that PDE4 inhibitors may well be of clinical utility in CLL or autoimmune diseases that are driven by TLR-mediated signaling (Tan et al., 2015). Here, TLR9 is linked to B-cell chronic lymphocytic leukemia.