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Introduction
Multiple myeloma (MM) is a B-cell neoplasia, characterized by the clonal expansion of malignant plasma cells in the bone marrow. During normal B-cell development, cells acquire expression of CD138, also known as syndecan-1 (SDC1), a marker highly specific for terminally differentiated normal plasma cells (1). CD138 is a heparin sulphate proteoglycan that controls tumor cell survival, growth, adhesion and bone cell differentiation in MM (2). Since CD138 is a specific surface antigen for MM cells and plasma cells in the bone marrow (3), it has been used for the purification of MM cells from clinical samples (4) and in the classification of MM cells in gene expression profiling analyses (5). In addition, the use of specific antibodies targeting CD138 are also considered as a novel treatment strategy for MM (6).
However, several studies have also reported decreased expression of CD138 in MM (7,8). Matsui et al, reported the existence of highly clonogenic MM cells lacking CD138 expression, and suggested that these cells may represent MM ‘stem cells’ (9). Furthermore, a decrease in CD138 expression has been observed during the course of clinical treatment in some patients. While high expression of CD138 is not consistently observed in myeloma cells, the significance of decreased CD138 expression in MM cells remains unclear.
In the present study, we investigated the expression of CD138 in primary MM cells by flow cytometry using the CD38 gating method (10), and analyzed the association between CD138 decrease and patient survival, retrospectively. To investigate the effects of decreased CD138 in MM, we utilized two MM cell lines with heterogeneous expression of CD138 (KYMM-1, CD138 low and KYMM-2, CD138 high). These cell lines were simultaneously established from the pleural effusion of an MM patient, who displayed a gradual reduction in CD138 expression during disease progression.
Materials and methods
MM patients and flow cytometric analysis
Flow cytometry data were obtained from 90 newly diagnosed and 15 relapsed or progressive MM patients, admitted to Kumamoto University Hospital, Kumamoto City Hospital and Hiroshima University Hospital. Written, informed consent was obtained according to the Declaration of Helsinki. Flow cytometry was performed by the commercially available CD38 multi-analysis (SRL Laboratories, Tokyo, Japan) by gating CD38 strong positive (++) fractions as previously described (10). To rule out the possibility...