Nonetheless, constitutive activation of NF-kB has been observed in most CLL samples [16, 17], and hyperactivation can be induced by inflammatory receptors, including Toll-like receptors (TLRs), which can be recapitulated in vitro by treating CLL cells with the TLR9 ligand CpG, either alone or in combination with a CD40 ligand and/or IL2 [11, 17–21]. This evidence concerns the gene TLR9 and B-cell chronic lymphocytic leukemia.