Previous studies have shown that CLL cells respond to the TLR9 agonist, CpG, with proliferation, upregulation of costimulatory molecules, and induction of apoptosis.[15], [16], [17] However, to our knowledge there has been no study to date that has evaluated the ability of these agents to induce CLL B cell differentiation into ISC. Here, TLR9 is linked to B-cell chronic lymphocytic leukemia.