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Expression and function of Fas (APO-1/CD95) in patient myeloma cells and
myeloma cell lines
JJ Westendorf, JM Lammert and DF Jelinek
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Cross-linkage of the Fas antigen induces programmed cell death in many
normal and malignant lymphoid cells by a process known as apoptosis. In
this study, we examined the sensitivity of myeloma cell lines and patient
plasma cells to a cytolytic anti-Fas monoclonal antibody (MoAb). Eight of
10 myeloma cell lines were induced to undergo programmed cell death by
anti-Fas MoAb as determined by DNA fragmentation and morphologic changes.
Of the two myeloma cell lines that were resistant to anti-Fas treatment,
one did not express the Fas antigen. Only the U266 cell line expressed Fas,
but was not killed by the anti0Fas MoAb. To extend these studies, we have
examined the expression and function of Fas in freshly isolated
CD38hiCD45neg-int plasma cells from patients with multiple myeloma (MM),
monoclonal gammopathy of undetermined significance (MGUS), and primary
amyloidosis (AL). By three-color flow cytometry, we found Fas expression in
CD38hiCD45neg-int plasma cells from all patient groups to be variable, as
Fas was expressed in 15 of 28 MM, 3 of 6 MGUS, and 2 of 7 AL patients. In
morphologic studies of apoptosis, Fas-positive myeloma cells in patient
bone marrow mononuclear cell (MNC) cultures appeared to be resistant to
anti-Fas-mediated apoptosis. By contrast, purified myeloma cells from the
same patient were sensitive to anti-Fas treatment, suggesting the presence
of a protective factor(s) in unseparated MNC cultures that may inhibit
Fas-induced apoptosis of plasma cells. Of interest, serum from normal
individuals and myeloma patients also protected myeloma cell lines from
undergoing Fas-mediated apoptosis. These studies show that Fas expression
in myeloma cell lines and CD38hiCD45neg-int patient plasma cells is
variable and may reflect a variance in the maturation status of the various
plasma cell populations. Moreover, Fas-mediated killing of patient cells
and myeloma cell lines was also variable, which may be influenced, in part,
by the presence of a soluble protective factor.
Volume 85,
Issue 12,
pp. 3566-3576,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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