SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders

Giorgia Simonetti, Maria Teresa Sabrina Bertilaccio, Tania Veliz Rodriguez, Benedetta Apollonio, Antonis Dagklis, Martina Rocchi, Anna Innocenzi, Stefano Casola, Thomas H. Winkler, Lars Nitschke, Maurilio Ponzoni, Federico Caligaris-Cappio, Paolo Ghia

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Abstract

The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to reduced turnover and increased proliferation and survival of murine B-1a cells. Siglecg-/- mice show a premature expansion of polyclonal CD5+ B cells in the spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in Siglecg-/- mice over time. We demonstrate that in aging animals SIGLEC-G deficiency promotes progressive accumulation of monoclonal B lymphocytes and increases the susceptibility to develop B-cell lymphoproliferative disorders. Lymphoid tumors arising in aged Siglecg-/- mice are monoclonal and histologically heterogeneous as they include diffuse large B-cell lymphoma, follicular lymphoma, and medium-to-large B-cell monomorphic lymphoma but surprisingly not chronic lymphocytic leukemia. The tumors express high levels of BCL-2 and are transplantable. In keeping with these findings we have also observed a remarkable down-regulation of the human ortholog SIGLEC10 in human B-cell lymphoma and leukemia cell lines. Taken together, these observations indicate that the down-regulation of negative B-cell receptor regulators such as SIGLEC-G/SIGLEC10 may represent another mechanism relevant to the pathogenesis of B-cell lymphomas.

Original languageEnglish
Pages (from-to)1356-1364
Number of pages9
JournalHaematologica
Volume99
Issue number8
DOIs
Publication statusPublished - Aug 1 2014

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ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

Simonetti, G., Sabrina Bertilaccio, M. T., Rodriguez, T. V., Apollonio, B., Dagklis, A., Rocchi, M., Innocenzi, A., Casola, S., Winkler, T. H., Nitschke, L., Ponzoni, M., Caligaris-Cappio, F., & Ghia, P. (2014). SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders. Haematologica, 99(8), 1356-1364. https://doi.org/10.3324/haematol.2013.100230