Article (Scientific journals)
Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Binsfeld, Marilène; Beguin, Yves; Belle, Ludovic et al.
2014In PLoS ONE, p. 113764
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Keywords :
Graft-versus-myeloma; multiple myeloma; GvHD; Allogeneic SCT; MOPC315.BM
Abstract :
[en] 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
Disciplines :
Hematology
Author, co-author :
Binsfeld, Marilène ;  Université de Liège - ULiège > GIGA-R : Hématologie
Beguin, Yves  ;  Université de Liège - ULiège > GIGA-R : Hématologie
Belle, Ludovic 
Otjacques, Eléonore ;  Université de Liège - ULiège > GIGA-R : Hématologie
HANNON, Muriel ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
BRIQUET, Alexandra ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Heusschen, Roy ;  Université de Liège - ULiège > GIGA-R : Hématologie
Drion, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R:Méth. expér.des anim. de labo et éth. en expér. anim.
Zilberberg, Jenny
Bogen, Bjarne
Baron, Frédéric  ;  Université de Liège - ULiège > GIGA-R : Hématologie
CAERS, Jo  ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Language :
English
Title :
Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Publication date :
2014
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Pages :
e113764
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 07 October 2014

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