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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1341-1345.
Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2004-11-4477.
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Submitted November 29, 2004
Accepted March 6, 2005
A SCID-hu in vivo model for human Waldenstrom macroglobulinemia
Pierfrancesco Tassone, Paola Neri, Jeffery L Kutok, Olivier Tournilhac, Daniel D Santos, Evdoxia Hatjiharissi, Vidit Munshi, Salvatore Venuta, Kenneth C Anderson, Steven P Treon, and Nikhil C Munshi*
Dana-Farber Cancer Institute, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA; University of 'Magna Graecia' and Cancer Center, Catanzaro, Italy, Italy
Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA
Dana-Farber Cancer Institute, Boston, MA, USA
VA Boston Healthcare System, Boston, MA, USA
University of 'Magna Graecia' and Cancer Center, Catanzaro, Italy, Italy
Dana-Farber Cancer Institute, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA
* Corresponding author; email: Nikhil_Munshi{at}dfci.harvard.edu.
The pre-clinical evaluation of investigational agents for Waldenstrom macroglobulinemia (WM) has been limited by the lack of in vivo models using explanted patient cells. We describe a novel in vivo model of human WM in immunodeficient mice implanted with human fetal bone chips (SCID-hu mice) into which WM cells from patient bone marrow are engrafted directly into the human bone marrow (huBM) microenvironment. WM cells in SCID-hu mice produced monoclonal human paraprotein (IgM and/or or chain) detectable in mice sera. Immunohistochemical analysis of human bone retrieved from SCID-hu mice showed infiltration with CD20+, IgM+, and monotypic light chain+ lymphoplasmacytic cells. Mast cells were observed to be associated with the infiltrate in these sections. Treatment of SCID-hu mice bearing WM with Rituximab induced tumor regression, associated with decreased of serum paraprotein. This model, therefore, recapitulates the in vivo biology of WM and allows the study of novel investigational drugs targeting WM cells in the huBM milieu.

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