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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2332-2336.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-09-3064.
Submitted September 5, 2003
Accepted November 7, 2003
Characterization of clonogenic multiple myeloma cells
William H Matsui*, Carol Ann Huff, Qiuju Wang, Matthew T Malehorn, James Barber, Yvette Tanhehco, B Douglas Smith, Curt I Civin, and Richard J Jones
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
* Corresponding author; email: matsuwi{at}jhmi.edu.
The identity of the cells responsible for the initiation and maintenance of multiple myeloma (MM) remains unclear largely because of the difficulty growing MM cells in vitro and in vivo. MM cell lines and clinical specimens are characterized by malignant plasma cells that express the cell surface antigen syndecan-1 (CD138); however, CD138 expression is limited to terminally differentiated plasma cells during B cell development. Moreover, circulating B cells that are clonally related to MM plasma cells have been reported in some patients with MM. We found that human MM cell lines contained small (< 5%) subpopulations that lacked CD138 expression and had greater clonogenic potential in vitro than corresponding CD138+ plasma cells. CD138neg cells from clinical MM samples were similarly clonogenic both in vitro and in NOD/SCID mice, whereas CD138+ cells were not. Furthermore, CD138neg cells from both cell lines and clinical samples phenotypically resembled post-germinal center B cells, and their clonogenic growth was inhibited by the anti-CD20 monoclonal antibody rituximab. These data suggest that MM "stem cells" are CD138neg B cells with the ability to replicate and subsequently differentiate into malignant CD138+ plasma cells.
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