Characterization of clonogenic multiple myeloma cells
Characterization of clonogenic multiple myeloma cells
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DOI：
10.1182/blood-2003-09-3064
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发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Jones, RJ
中科院分区：
文献类型：
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作者：
Matsui, W;Huff, CA;Jones, RJ
多发性骨髓瘤(MM)的发生和维持在很大程度上是由于MM细胞在体外和体内的生长困难，导致MM发生和维持的细胞身份尚不清楚。MM细胞系和临床标本以表达细胞表面抗原Syndecan-1(CD138)的恶性浆细胞为特征；然而，CD138的表达仅限于B细胞发育过程中终末分化的浆细胞。此外，在一些MM患者中也发现了与MM浆细胞克隆性相关的循环B细胞。我们发现，人MM细胞系含有少量(<；5%)缺乏CD138表达的亚群，并且在体外比相应的CD138(+)浆细胞具有更大的克隆性。临床MM标本中的CD138(-)细胞在体外和非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠中具有类似的克隆性，而CD138(+)细胞则不能。此外，CD138(-)细胞株和临床标本的表型与生发中心B细胞相似，其克隆性生长可被抗CD20单抗利妥昔单抗抑制。这些数据表明，多发性骨髓瘤“干细胞”是CD138(-)B细胞，具有复制和随后分化为恶性CD138(+)浆细胞的能力。(C)2004年，由美国血液病学会提供。
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. (C) 2004 by The American Society of Hematology.