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

Alessandro Poggi (1) , Claudia Prevosto (2) , Silvia Catellani (3) , Ilaria Rocco (4) , Anna Garuti (4) , Maria Raffaella Zocchi (5)

1 Translational Oncology
2 Translational Oncology
3 Department of Clinical Oncology and Haematology
4 Department of Internal Medicine Medical Specialties
5 Division of Immunology, Transplants and Infectious Diseases

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.

Mots clés: Medicine

Alessandro Poggi, Claudia Prevosto, Silvia Catellani, Ilaria Rocco, Anna Garuti, et al.. Engagement of CD31 delivers an activating signal that contributes to the survival of chronic lymphocytic leukemia cells.. British Journal of Haematology, 2010, 151 (3), pp.252. ⟨10.1111/j.1365-2141.2010.08343.x⟩. ⟨hal-00573089⟩