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

Authors
  • Simonetti, Giorgia
  • Bertilaccio, Maria Teresa Sabrina
  • Rodriguez, Tania Veliz
  • Apollonio, Benedetta
  • Dagklis, Antonis
  • Rocchi, Martina
  • Innocenzi, Anna
  • Casola, Stefano
  • Winkler, Thomas H
  • Nitschke, Lars
  • Ponzoni, Maurilio
  • Caligaris-Cappio, Federico
  • Ghia, Paolo
Type
Published Article
Journal
Haematologica
Publisher
Ferrata Storti Foundation
Publication Date
Aug 01, 2014
Volume
99
Issue
8
Pages
1356–1364
Identifiers
DOI: 10.3324/haematol.2013.100230
PMID: 24859880
Source
Medline
License
Unknown

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.

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