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SUMMARY:An important issue in myeloma is that focal lesions are often the site of relapse, and the disease may reappear at sides of focal lesions after complete remission (CR). He suggested that these focal lesions retain dormant myeloma cells that cannot be detected by current tests defining CR. Once myeloma-associated osteolytic lesions appear they do not heal, and the reasons for repair are not known, although it could be that the microenvironment is exhausted or there are undetectable residual tumor cells present. This lack of healing is specific to myeloma; healing is seen in osteolytic lesions associated with other tumor types. The SCID-hu model of SCID mice implanted with human fetal bone (generally half a tibia or femur) was developed to identify the cell responsible for myeloma growth and relapse and to study the microenvironment. Whole bone marrow or purified plasma cells from patients with myeloma are injected into the implanted bone. In this system only myeloma cells and no other classes of cells proliferate. If two bones are implanted and only one injected with myeloma cells, the cells will migrate to the non-injected bone, and both bones will display lytic lesions. Dr. Epstein’s group has transferred myeloma cells after establishment in one animal to a second, third, and fourth animal. The cells do not change phenotype or mature, and their CD138+ phenotype is maintained. No other cell can or is required to produce myeloma in this system. Whether there is a myeloma stem cell or a recycled myeloma cell that gives rise to myeloma in this system is still under debate.
by Lynne Lederman, PhD