Characterization of clonogenic multiple myeloma cells

William Matsui, Carol Ann Huff, Qiuju Wang, Matthew T. Malehorn, James Barber, Yvette Tanhehco, B. Douglas Smith, Curt I. Civin, Richard J. Jones

Research output: Contribution to journalArticle

Abstract

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. CD138 - cells from clinical MM samples were similarly clonogenic both in vitro and in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, whereas CD138+ cells were not. Furthermore, CD138- calls from both cell lines and clinical samples phenotypically resembled postgerminal center B cells, and their clonogenic growth was inhibited by the anti-CD20 monoclonal antibody rituximab. These data suggest that MM "stem cells" are CD138- 8 cells with the ability to replicate and subsequently differentiate into malignant CD138+ plasma cells.

Original languageEnglish (US)
Pages (from-to)2332-2336
Number of pages5
JournalBlood
Volume103
Issue number6
DOIs
StatePublished - Mar 15 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Matsui, W., Huff, C. A., Wang, Q., Malehorn, M. T., Barber, J., Tanhehco, Y., Smith, B. D., Civin, C. I., & Jones, R. J. (2004). Characterization of clonogenic multiple myeloma cells. Blood, 103(6), 2332-2336. https://doi.org/10.1182/blood-2003-09-3064