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

Alessandro Poggi, Claudia Prevosto, Silvia Catellani, Ilaria Rocco, Anna Garuti, Maria R. Zocchi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)252-264
Number of pages13
JournalBritish Journal of Haematology
Volume151
Issue number3
DOIs
Publication statusPublished - Nov 2010

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Keywords

  • Bax
  • Bcl-2
  • Bcl-x
  • NF-kB.
  • PECAM-1

ASJC Scopus subject areas

  • Hematology

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