MYELOMA CELLS EXPRESS FAS ANTIGEN APO-1 (CD95) BUT ONLY SOME ARE SENSITIVE TO ANTI-FAS ANTIBODY RESULTING IN APOPTOSIS

To find out which cytokines are involved in the pathogenesis of multip le myeloma, we investigated cytokine receptor expression on myeloma ce lls using a panel of monoclonal antibodies (MoAbs). Flow cytometric an alysis of five myeloma cell lines (RPMI8226, ARH77, KMM-1, U266, and H s) and myeloma cells freshly isolated from eight patients showed that interleukin-1 receptor (IL-1R) type I and type II, IL-2 alpha and beta chains, IL-4R, IL-6R, IL-7R, IL-8R, granulocyte macrophage colony-sti mulating factor receptor (GM-CSFR). c-kit (stem cell factor receptor [ SCFR]), membrane bound stem cell factor (MBSCF). and tumor necrosis fa ctor (TNF) receptors type I and type II were not always detected on th e myeloma cells. However, interferon-gamma receptor, gp130, and Fas an tigen were constitutively expressed, except one sample. To determine t he role of Fas antigen on myeloma cells, these cells were cultured wit h anti-fas MoAb. Apoptotic changes characterized by loss of cell volum e, membrane blebbing, fragmentation of nuclei, and condensed chromatin were observed in three of five myeloma cell lines. When bcl-2 express ion was examined, it was seen in all the cell lines regardless of the sensitivity to anti-Fas MoAb. Furthermore, anti-Fas MoAb not only indu ced apoptosis of freshly isolated myeloma cells but also inhibited the DNA synthesis, although such effects varied from patient to patient. The data indicate that only some myeloma cells undergo apoptosis in re sponse to the signal mediated by the Fas antigen. (C) 1995 by The Amer ican Society of Hematology.