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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2935-2945. Prepublished online as a Blood First Edition Paper on June 5, 2008; DOI 10.1182/blood-2008-02-142430. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-142430v1 112/7/2935    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kirshner, J. Articles by Pilarski, L. M. Search for Related Content PubMed PubMed Citation Articles by Kirshner, J. Articles by Pilarski, L. M. Related Collections Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma Julia Kirshner1, Kyle J. Thulien1, Lorri D. Martin1, Carina Debes Marun1, Tony Reiman1, Andrew R. Belch1, and Linda M. Pilarski1 1 Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, AB Although the in vitro expansion of the multiple myeloma (MM) clone has been unsuccessful, in a novel three-dimensional (3-D) culture model of reconstructed bone marrow (BM, n = 48) and mobilized blood autografts (n = 14) presented here, the entire MM clone proliferates and undergoes up to 17-fold expansion of malignant cells harboring the clonotypic IgH VDJ and characteristic chromosomal rearrangements. In this system, MM clone expands in a reconstructed microenvironment that is ideally suited for testing specificity of anti-MM therapeutics. In the 3-D model, melphalan and bortezomib had distinct targets, with melphalan targeting the hematopoietic, but not stromal com-partment. Bortezomib targeted only CD138+CD56+ MM plasma cells. The localization of nonproliferating cells to the reconstructed endosteum, in contact with N-cadherin–positive stroma, suggested the presence of MM-cancer stem cells. These drug-resistant CD20+ cells were enriched more than 10-fold by melphalan treatment, exhibited self-renewal, and generated clonotypic B and plasma cell progeny in colony forming unit assays. This is the first molecularly verified demonstration of proliferation in vitro by ex vivo MM cells. The 3-D culture provides a novel biologically relevant preclinical model for evaluating therapeutic vulnerabilities of all compartments of the MM clone, including presumptive drug-resistant MM stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Myeloma research goes 3D Diane F. Jelinek Blood 2008 112: 2600-2601. [Full Text] [PDF] This article has been cited by other articles: T. M. Tancred, A. R. Belch, T. Reiman, L. M. Pilarski, and J. Kirshner Altered Expression of Fibronectin and Collagens I and IV in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance J. Histochem. Cytochem., March 1, 2009; 57(3): 239 - 247. [Abstract] [Full Text] [PDF] B. J. Taylor, J. Kriangkum, J. A. Pittman, M. J. Mant, T. Reiman, A. R. Belch, and L. M. Pilarski Analysis of clonotypic switch junctions reveals multiple myeloma originates from a single class switch event with ongoing mutation in the isotype-switched progeny Blood, September 1, 2008; 112(5): 1894 - 1903. [Abstract] [Full Text] [PDF]

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