The CD49d/CD29 complex is physically and functionally associated with CD38 in B-cell chronic lymphocytic leukemia cells

A. Zucchetto, T. Vaisitti, D. Benedetti, E. Tissino, V. Bertagnolo, D. Rossi, R. Bomben, M. Dal Bo, M. I. Del Principe, A. Gorgone, G. Pozzato, G. Gaidano, G. Del Poeta, F. Malavasi, S. Deaglio, V. Gattei

Research output: Contribution to journalArticlepeer-review

Abstract

CD49d and CD38 are independent negative prognostic markers in chronic lymphocytic leukemia (CLL). Their associated expression marks a disease subset with a highly aggressive clinical course. Here, we demonstrate a constitutive physical association between the CD49d/CD29 integrin complex and CD38 in primary CLL cells and B-cell lines by (i) cocapping, (ii) coimmunoprecipitation and (iii) cell adhesion experiments using CD49d-specific substrates (vascular-cell adhesion molecule-1 or CS-1/H89 fibronectin fragments). The role of CD38 in CD49d-mediated cell adhesion was studied in CD49d CD38 and CD49d + CD38 - primary CLL cells, and confirmed using CD38 transfectants of the originally CD49d + CD38 - CLL-derived cell line Mec-1. Results indicate that CD49d + CD38 - cells adhered more efficiently onto CD49d-specific substrates than CD49d CD38 cells (P0.001). Upon adhesion, CD49d + CD38 - cells underwent distinctive changes in cell shape and morphology, with higher levels of phosphorylated Vav-1 than CD49d + CD38 - cells (P0.0006) and a more complex distribution of F-actin to the adhesion sites. Lastly, adherent CD49d + CD38 - cells were more resistant to serum-deprivation- induced (P0.001) and spontaneous (P0.03) apoptosis than the CD49d + CD38 -s counterpart. Altogether, our results point to a direct role for CD38 in enhancing CD49d-mediated adhesion processes in CLL, thus providing an explanation for the negative clinical impact exerted by these molecules when coexpressed in neoplastic cells.

Original languageEnglish
Pages (from-to)1301-1312
Number of pages12
JournalLeukemia
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 2012

Keywords

  • CD38
  • CD49d
  • chronic lymphocytic leukemia
  • CLL
  • integrins

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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