Kuribayashi N, Hata H, Matsuzaki H, Yoshida M, Sonoki T, Nagasaki A, Kimura T, Harada N, Takatsuki K
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Med Oncol. 1998 Dec;15(4):248-54. doi: 10.1007/BF02787208.
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.
骨髓瘤细胞对美法仑（左旋苯丙氨酸氮芥，L-PAM）的耐药性是一个严重问题。为了研究耐药机制，我们制备了一种针对耐美法仑骨髓瘤细胞KHM-11R的单克隆抗体，克隆O3。蛋白质免疫印迹分析表明，O3抗原的分子量约为90 kDa。KHM-11R中O3抗原的表达比亲代美法仑敏感细胞系KHM-11高约两倍。O3在浆细胞系、B细胞系和单核细胞系中优先表达，但在T细胞系中不表达。对骨髓瘤患者骨髓样本的分析显示，23个样本中有13个在不同水平表达O3抗原，并且患者中O3抗原的表达与先前的化疗、晚期临床分期以及骨髓瘤细胞的髓外浸润相关。此外，诊断时表达O3抗原的患者预后往往较差。对骨髓瘤细胞中O3抗原的研究将有助于揭示髓外浸润的病理生理学以及美法仑的细胞杀伤机制。
