Activation molecules on human myeloma cells.

Abstract

IL-6 is now recognized as a major survival and proliferation factor for murine and human malignant plasma cells (Klein et al 1995; Lattanzio et al 1997). This is especially true for patients with terminal multiple myeloma and extramedullar proliferation. In these patients, we and others have shown the possibility to reproducibly obtain cell lines whose survival and proliferation are dependent on addition of exogenous IL-6, and more generally of cytokines of the IL-6 family (Zhang et al 1994; Westendorf et al 1996; Jernberg et al 1987). Using these cell lines, cytokines other than IL-6 were recognized as myeloma cell survival or proliferation factors, namely interferon-alpha (Ferlin-Bezombes et al 1998), tumor necrosis factor (Jourdan et al 1999), insulin growth factor (Georgii-Hemming et al 1996; Jelineka/ 1997) or hepatocyte growth factor (Borset et al 1996). In patients with chronic disease and a medullary involvement, primary myeloma cells survive and slightly proliferate when cultured for several days together with bone marrow stromal cells. IL-6 is highly produced in these cultures by stromal cells (Portier et al 1991) and controls the slight proliferation of myeloma cells since anti-IL-6 antibodies inhibit it (Klein et al 1989). However, IL-6 alone is not sufficient to trigger the survival of primary myeloma cells from patients with chronic disease. Indeed, when these primary myeloma cells were highly purified, 60–80% of myeloma cells died by apoptosis within 2 days of culture (Fig. 1).