SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders
Simonetti G, Bertilaccio MTS, Rodriguez TV, Apollonio B, Dagklis A, Rocchi M, Innocenzi A, Casola S, Winkler T, Nitschke L, Ponzoni M, Caligaris-Cappio F, Ghia P (2014)
Publication Status: Published
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: FERRATA STORTI FOUNDATION
Book Volume: 99
Pages Range: 1356-1364
Journal Issue: 8
DOI: 10.3324/haematol.2013.100230
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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APA:
Simonetti, G., Bertilaccio, M.T.S., Rodriguez, T.V., Apollonio, B., Dagklis, A., Rocchi, M.,... 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
MLA:
Simonetti, Giorgia, et al. "SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders." Haematologica 99.8 (2014): 1356-1364.
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