Finally, we applied CpG as a ligand to activate TLR signaling in CLL cells, as is shown by gene expression studies in LN-derived CLL cells,17,18 which may further promote the upregulation of cytokine receptors.19 Although the exact in vivo TLR9 ligand remains unknown, a recent study indicated a role of cell-free mitochondrial DNA in plasma from CLL patients, which can trigger TLR9 signaling in a similar fashion to CpG.20 The gene discussed is TLR9; the disease is B-cell chronic lymphocytic leukemia.