[The mechanisms of myeloma cell growth]

The mechanism of human multiple myeloma cell growth was studied utilizing twelve myeloma cell lines established in vitro. Seven of them were derived from extramedullary lesions and had the appearance of immature plasmablast. Five were from bone marrow and showed typical plasma cell morphology. Seven extramedullary lesion derived cell lines grew spontaneously and additively proliferated in response to IL-6 and/or gp-130 related cytokines. Three bone marrow derived cell lines grew dependently on a macrophage feeder layer and then on IL-6. Two bone marrow derived cell lines grew in the presence of bone marrow stromal cells or stromal cell culture supernatant, however, they did not proliferate in response to IL-6. While establishing cell lines, it was found that the proliferating fraction was primarily included in a fraction which was non-adherent to stromal cells and was composed of undifferentiated plasmablasts. Undifferentiated plasmablasts proliferated in response to IL-6, while the adherent and mature form of myeloma cells did not proliferate in response to IL-6. Two established bone marrow derived stromal cell dependent myeloma cell lines were adherent to stromal cells, had the mature form of plasma cell morphology and did not proliferate in response to IL-6. These results imply that multiple myeloma cells are composed of heterogenous populations with different maturities and different growth mechanisms.