Establishment of a monoclonal antibody to human myeloma cell: relation to chemotherapy and extramedullar infiltration

Resistance of myeloma cells to melphalan (L-PAM) is a serious problem. To i nvestigate mechanisms of drug resistance, we generated a monoclonal antibod y, done O3, to melphalan-resistant myeloma cells, KHM-11R. Western blot ana lysis 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 e xpressed in plasma cell, B-cell, and monocytic cell lines, but not in T-cel l lines. Analysis of bone marrow samples from myeloma patients revealed tha t 13 of 23 samples expressed O3 antigen at various levels, and that O3 anti gen expression in patients correlate with preceding chemotherapy, advanced clinical stage and extramedullar invasion of myeloma cells. Furthermore, pa tients expressing O3 antigen at the time of diagnosis tended to have poor p rognosis. The investigation of O3 antigen in myeloma cells will be useful t o reveal the pathophysiology of extramedullar invasion and the mechanism of cell killing by melphalan.