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See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Binsfeld, Marilène ULg; Beguin, Yves ULg; Belle, Ludovic et al

in PLoS ONE (in press)

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic ... [more ▼]

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) has remained controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice (previously injected with the MOPC315.BM myeloma cell line), based on a chronic graft-versus-host disease (GvHD) murine model. Methods and results: Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received 30 days later an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplantation by intravenous administration of bone marrow cells and splenocytes. We observed a graft-versus-myeloma effect in 94% of the allogeneic transplanted mice, as luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma evolution. Lower serum paraprotein levels and myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect, while allogeneic mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggest the involvement of effector memory CD4 and CD8 T cells in the GvM effect. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR V spectratyping analysis identified V families within CD4 and CD8 T cells which were associated with both GvM effects and GVHD, whereas other V families within CD4 T cells were associated exclusively with either GvM or GvHD responses. Conclusions: We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first immunocompetent murine model which is based on a MM model closely resembling human MM disease (bone marrow tropism, ...) and using allo-SCT after the disease establishment, as a curative treatment [less ▲]

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See detailGammapathie monoclonale de signification indéterminée : information destinée aux médecins référents
CAERS, Jo ULg; Binsfeld, Marilène ULg; Muller, Joséphine ULg et al

in Revue Médicale de Liège (in press)

Les gammapathies monoclonales de signification indéterminée (GMSI) sont fréquentes dans la population générale. Leur potentiel évolutif malin impose une surveillance clinique régulière et prolongée ... [more ▼]

Les gammapathies monoclonales de signification indéterminée (GMSI) sont fréquentes dans la population générale. Leur potentiel évolutif malin impose une surveillance clinique régulière et prolongée. Cependant, les GMSI forment un groupe très hétérogène et tous les patients n’ont pas le même risque de transformation maligne. Plusieurs critères biologiques simples, disponibles en routine ont été identifiés comme facteurs prédictifs de la transformation. Les scores prédictifs de transformation maligne combinant plusieurs de ces facteurs permettront probablement la classification des patients en fonction de leur risque évolutif. La prise en charge pourra ainsi être adaptée au risque individuel de chaque patient [less ▲]

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See detailGalectins in cancer: jacks of all trades
Heusschen, Roy ULg; Schulkens, Iris; Muller, Joséphine ULg et al

in International Journal of Molecular Medicine (2014)

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See detailCellular immunotherapy in multiple myeloma : lessons from preclinical models
Binsfeld, Marilène ULg; Fostier, K.; Muller, Joséphine ULg et al

in Biochimica et Biophysica Acta - Reviews on Cancer (2014), 1846

The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and ... [more ▼]

The majority of multiple myeloma patients relapse with the current treatment strategies, raising the need for alternative therapeutic approaches. Cellular immunotherapy is a rapidly evolving field and currently being translated into clinical trials with encouraging results in several cancer types, including multiple myeloma. Murine multiple myeloma models are of critical importance for the development and refinement of cellular immunotherapy. In this review,we summarize the immune cell changes that occur inmultiplemyelomapatients and we discuss the cell-based immunotherapies that have been tested in multiple myeloma, with a focus on murine models. [less ▲]

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See detailGalectin expression in the multiple myeloma microenvironment
Muller, Joséphine ULg; CAERS, Jo ULg; Binsfeld, Marilène ULg et al

in Belgian Journal of Hematology (2014)

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See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.
Binsfeld, Marilène ULg; BEGUIN, Yves ULg; Belle, Ludovic et al

in Belgian Journal of Hematology (2014)

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See detailMultiple myeloma cells instruct myeloid-derived suppressor cells to release pro-angiogenic cytokines
Binsfeld, Marilène ULg; Heusschen, Roy ULg; Lamour, Virginie et al

in Belgian Journal of Hematology (2014)

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See detailLe myélome multiple asymptomatique : le paysage thérapeutique change
CAERS, Jo ULg; BEGUIN, Yves ULg

in Oncol. Hematol. (2014), 8

Le myélome multiple est le deuxième cancer hématologique en termes de fréquence avec plus de 700 nouveaux cas chaque année en Belgique. Le myélome asymptomatique, ou smoldering mye/omo, est un stade ... [more ▼]

Le myélome multiple est le deuxième cancer hématologique en termes de fréquence avec plus de 700 nouveaux cas chaque année en Belgique. Le myélome asymptomatique, ou smoldering mye/omo, est un stade précurseur du myélome multiple. En moyenne, les patients présentant un myélome asymptomatique ont un risque annuel de progression en myélome déclaré de 10%. Différents facteul"s ont été combinés dans des modélisations pronostiques: le rapport des chaînes légères, les anomalies radiologiques, la présence d'une gammapathie évolutive et l'infiltration médullaire > 60% ont récemment été identifiés comme facteurs prédictifs d'une progression précoce pour lesquels certains auteurs évoquent la mise en roùte d'un traitement anti-myélome. Cette stratégie thérapeutique précoce a démontré son efficacité dans une étude randomisée qui comparait un traitement par lénalidornide et dexaméthasone avec une approche attentiste chez des patients à risque. [less ▲]

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See detailDiagnosis and follow-up of monoclonal gammopathies of undetermined significance; information for referring physicians.
CAERS, Jo ULg; Vekemans, Marie-Christiane; Bries, Greet et al

in Annals of Medicine (2013), 45

The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a ... [more ▼]

The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a preneoplastic entity that can transform into multiple myeloma or other lymphoproliferative disorders. The risk of malignant transformation is estimated at 1% per year and persists over time. Predictors of malignant transformation have been identified such as the heavy chain isotype, the monoclonal component level, increasing levels of M-protein during the first years of follow-up, bone marrow plasmocytosis, dosage of serum free light chains, the presence of immunophenotypic abnormal plasma cells, aneuploidy and the presence of circulating plasma cells. Prognostic scores that combine certain of these factors have been proposed and allow the identification of high-risk patients. Their use could assist in tailoring the care for each patient, based on his/her risk profile. [less ▲]

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See detailPlasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group.
Fernández de Larrea, C; Kyle, RA; Durie, BG et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2013), 27(4), 780-91

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See detailA novel mutation in the CUB sequence of matriptase-2 (TMPRSS6) is implicated in iron-resistant iron deficiency anaemia (IRIDA).
JASPERS, Aurélie ULg; CAERS, Jo ULg; LE GAC, Gerald et al

in British Journal of Haematology (2013), 160(4), 564-565

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See detailImage of the month: Hairy kidneys
Cornet, G; GRAYET, Benjamin ULg; Godon, A et al

in Revue Médicale de Liège (2013), 68(1), 4-5

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See detailGammapathies monoclonales de signification indéterminée
Vekemans, Marie-Christiane; CAERS, Jo ULg; Doyen, Chantal et al

in Louvain Medical (2013), 132(2), 51-62

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