title: 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.
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy Università degli Studi di Milano-Bicocca, Milano, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Simonetti
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Maria Teresa Sabrina
authors.initials: MT
authors.lastname: Bertilaccio
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Tania Veliz
authors.initials: TV
authors.lastname: Rodriguez
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Apollonio
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Antonis
authors.initials: A
authors.lastname: Dagklis
authors.affiliation: Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Rocchi
authors.affiliation: Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Innocenzi
authors.affiliation: The Institute of Molecular Oncology (IFOM) of the Italian Foundation for Cancer Research (FIRC), Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.affiliation: Department of Biology, Nikolaus Fiebiger Center for Molecular Medicine, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
authors.affiliation: Department of Biology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.affiliation: Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milano, Italy Clinical Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy Clinical Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milano, Italy Vita-Salute San Raffaele University, Milano, Italy caligaris.federico@hsr.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milano, Italy Clinical Unit of Lymphoid Malignancies, Department of Oncology, San Raffaele Scientific Institute, Milano, Italy Vita-Salute San Raffaele University, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D037102:Lectins / Q000172:deficiency* / Q000235:genetics; D015448:Leukemia, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency* / Q000235:genetics; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse