Engagement of CD31 delivers an activating signal that contributes to the survival of chronic lymphocytic leukemia cells.

International audience ; Herein we show that engagement of CD31 delivers a survival signal in chronic lymphocytic leukaemia (CLL) cells. We describe two groups of CLL, showing a different kinetics of apoptosis in vitro and distinct ratios between anti-apoptotic and pro-apoptotic proteins: CLL-I displayed low Bcl-xL/Bax and Bcl-2/Bax ratio and underwent rapid apoptosis in vitro; CLL-II had high Bcl-xL/Bax and Bcl-2/Bax ratio and were resistant to apoptosis for several days. Nurse-like cells, expressing vimentin, CD68 and CD31 were detected mainly in CLL-II cultures. Of note, CD31 cross-linking, obtained with a specific monoclonal antibody (mAb), induced PI-3K-dependent Akt phosphorylation and nuclear translocation of the NF-kBp65 and p52 subunits in both CLL groups, leading to up-regulation of Bcl-2 and Bcl-xL transcription and increased cell survival. Binding to CD31+ stable transfectants, could also deliver an anti-apoptotic signal in B cells of both CLL-I and CLL-II, increasing the Bcl-2 and Bcl-xL protein content, regardless the expression of CD38. On the other hand, the addition of the F(ab')2 (that is unable to oligomerize the target molecule) of the anti-CD31 mAb prevented these effects. These data suggest that CD31 adhesion system may play a role also in vivo in maintaining CLL survival.