Establishment of a monoclonal antibody to human myeloma cell: relation to chemotherapy and extramedullar infiltration |
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Authors: | Noriomi Kuribayashi Hiroyuki Hata Hiromitsu Matsuzaki Minoru Yoshida Takashi Sonoki Akitoshi Nagasaki Tatsuya Kimura Naoko Harada and Kiyoshi Takatsuki |
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Institution: | (1) Second Department of Internal Medicine, Kumamoto University School of Medicine, Honjo 1-1-1, 860-8556 Kumamoto, Japan |
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Abstract: | Resistance of myeloma cells to melphalan (L-PAM) is a serious problem. To investigate mechanisms of drug resistance, we generated
a monoclonal antibody, clone O3, to melphalan-resistant myeloma cells, KHM-11R. Western blot analysis showed that molecular
weight of O3 antigen was approximately 90 kDa. Expression of O3 antigen was approximately two times higher in KHM-11R than
in parental melphalan sensitive cell line, KHM-11. O3 was preferentially expressed in plasma cell, B-cell, and monocytic cell
lines, but not in T-cell lines. Analysis of bone marrow samples from myeloma patients revealed that 13 of 23 samples expressed
O3 antigen at various levels, and that O3 antigen expression in patients correlate with preceding chemotherapy, advanced clinical
stage and extramedullar invasion of myeloma cells. Furthermore, patients expressing O3 antigen at the time of diagnosis tended
to have poor prognosis. The investigation of O3 antigen in myeloma cells will be useful to reveal the pathophysiology of extramedullar
invasion and the mechanism of cell killing by melphalan. |
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Keywords: | multiple myeloma monoclonal antibody melphalan drug resistance |
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