Differential responses to TLR and NOD2 stimulation in stereotyped CLL subset #1 versus #4. (A) Stimulation of TLR9, TLR1/2, TLR2/6, and NOD2 with the respective ligands strongly upregulated CD86 expression in subset #4 cases, whereas the same treatment had minimal or no effects on subset #1 cases. In contrast, stimulation of the TLR7 with imiquimod led to a much stronger upregulation of CD25 expression in subset #1 versus subset #4 cases. Whisker boxes (min to max) for statistically significant differences. Before statistical analysis values were normalized to the unstimulated controls. C, CpG ODN 2006; P, Pam3CSK4; M, MALP-2; MD, MDP; IM, imiquimod. (B) TLR9, TLR1/2, TLR2/6 and NOD2 stimulation with the respective ligands differentially regulates CLL cell apoptosis in subset #1 versus subset #4 cases. Each column corresponds to a different case. CpG, ODN 2006; PAM, Pam3CSK4; MALP, MALP-2; *p < 0.05, **p < 0.005.