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

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.

journal_name

Haematologica

journal_title

Haematologica

authors

Simonetti G,Bertilaccio MT,Rodriguez TV,Apollonio B,Dagklis A,Rocchi M,Innocenzi A,Casola S,Winkler TH,Nitschke L,Ponzoni M,Caligaris-Cappio F,Ghia P

doi

10.3324/haematol.2013.100230

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

1356-64

issue

8

eissn

0390-6078

issn

1592-8721

pii

haematol.2013.100230

journal_volume

99

pub_type

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