B-Cell Anergy and indolent clinical behavior Of CLL
Ntoufa S, Papakonstantinou N, Apollonio B, et al.
Key Points:
- Authors tested hypothesis "CLL SS4 cells (mutated IGHV4-34/IGKV2-30 BcRs, SS4) may exist in anergic state showing attenuated responses to selecting (auto)antigenic elements"
- 9/10 SS4 cases expressed high pERK levels, with no effect on BcR stimulation
- Serial analysis over 5-7 years revealed consistently positive pERK expression
- TLR1/2 stimulation up-regulated pERK levels, BcR crosslinking in TLR1/2-pretreated cells induced even higher pERK levels
- TLR1/2 stimulation up-regulates miR-17~92 cluster eventually leading to down-regulation of critical BcR and/or TLR signaling molecules
Implications:
- SS4 CLL clones anergic through BcR possibly because of chronic (auto)antigen activation and stimulation through TLR1/2 may break B-cell anergy
- TLR1/2 signals possibly induce miR-17~92 cluster up-regulation, leading to down-regulation of critical BcR and/or TLR signaling molecules and eventual modulation of ERK phosphorylation, a key to anergic state.
View the original abstract on the ASH website.
