TY - JOUR
T1 - Engagement of CD31 delivers an activating signal that contributes to the survival of chronic lymphocytic leukaemia cells
AU - Poggi, Alessandro
AU - Prevosto, Claudia
AU - Catellani, Silvia
AU - Rocco, Ilaria
AU - Garuti, Anna
AU - Zocchi, Maria R.
PY - 2010/11
Y1 - 2010/11
N2 - The present study showed that engagement of CD31 delivers a survival signal in chronic lymphocytic leukaemia (CLL) cells. We describe two groups of CLL, showing different kinetics of apoptosis in vitro and distinct ratios between anti-apoptotic and pro-apoptotic proteins: CLL-I displayed low Bcl- x
L/Bax and Bcl-2/Bax ratio and underwent rapid apoptosis in vitro; CLL-II had high Bcl-x
L/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 phosphatidylinositol- 3-kinase-dependent Akt phosphorylation and nuclear translocation of the nuclear factor-kBp65 and p52 subunits in both CLL groups, leading to upregulation of Bcl-2 and Bcl-x
L 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-x
L 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 the CD31 adhesion system may play a role also in vivo in maintaining CLL survival.
AB - The present study showed that engagement of CD31 delivers a survival signal in chronic lymphocytic leukaemia (CLL) cells. We describe two groups of CLL, showing different kinetics of apoptosis in vitro and distinct ratios between anti-apoptotic and pro-apoptotic proteins: CLL-I displayed low Bcl- x
L/Bax and Bcl-2/Bax ratio and underwent rapid apoptosis in vitro; CLL-II had high Bcl-x
L/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 phosphatidylinositol- 3-kinase-dependent Akt phosphorylation and nuclear translocation of the nuclear factor-kBp65 and p52 subunits in both CLL groups, leading to upregulation of Bcl-2 and Bcl-x
L 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-x
L 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 the CD31 adhesion system may play a role also in vivo in maintaining CLL survival.
KW - Bax
KW - Bcl-2
KW - Bcl-x
KW - NF-kB.
KW - PECAM-1
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U2 - 10.1111/j.1365-2141.2010.08343.x
DO - 10.1111/j.1365-2141.2010.08343.x
M3 - Article
C2 - 20813004
AN - SCOPUS:79952111400
VL - 151
SP - 252
EP - 264
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 3
ER -