Characterization of clonogenic multiple myeloma cells.
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- cells 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- B cells with the ability to replicate and subsequently differentiate into malignant CD138+ plasma cells.
Matsui
William
W
Sidney Kimmel Comprehensive Cancer Center, John Hopkins University School of Medicine, Bunting-Blaustein Cancer Research Bldg, Rm 245, 1650 Orleans St, Baltimore, MD 21231, USA. matsuwi@jhmi.edu
Huff
Carol Ann
CA
Wang
Qiuju
Q
Malehorn
Matthew T
MT
Barber
James
J
Tanhehco
Yvette
Y
Smith
B Douglas
BD
Civin
Curt I
CI
Jones
Richard J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D018952:Antigens, CD34 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000473:pathology* / Q000502:physiology; D015415:Biomarkers; D002999:Clone Cells; D006801:Humans; D016130:Immunophenotyping; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000473:pathology*; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000235:genetics; D000069283:Rituximab; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D015415:Biomarkers; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D000069283:Rituximab