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Growth arrest and terminal differentiation of leukemic myelomonocytic cells
induced through ligation of surface CD23 antigen
F Ouaaz, B Sola, F Issaly, JP Kolb, F Davi, F Mentz, M Arock, N Paul-Eugene, M Korner and B Dugas, et al
Molecular Immuno-Hematology Group, Pitie-Salpe-triere Hospital, Paris,
France.
Acute myelogenous leukemia (AML) cells express CD23 surface antigen after
in vitro treatment with various cytokines, including interleukin- 4 (IL-4)
and interferon gamma. Subsequent ligation of CD23 by specific monoclonal
antibody (MoAb) induces substantial morphologic and functional
modifications in these cells. In the present study, we investigated the
role of CD23 in the proliferation and the maturation of leukemic cells from
AML patients or the U937 cell line. CD23+ cell treatment with CD23 MoAb
inhibited the proliferation of leukemic cells. This correlated with their
terminal differentiation after 7 to 9 days incubation because they (1)
definitively lost their growth capacity; (2) adhered to culture flasks and
became monocyte/macrophage-like; and (3) expressed mature monocyte markers
including nonspecific esterases. Intracellular mechanism of this
antitumoral effect was then analyzed in U937 cells. Induction of
high-density surface CD23 expression by IL-4 or granulocyte-macrophage
colony-stimulating factor coincided with a transient decrease of U937 cell
proliferation. CD23 ligation during this low-proliferative phase induced a
rapid activation of L-arginine- dependent pathway and the intracellular
accumulation of cyclic guanosine monophosphate and cyclic adenosine
monophosphate (cAMP). Induction of these early messengers was followed by
the activation of nuclear factor-kB transcription factor and the modulation
of proto- oncogene expression by U937 cells. Whereas U937 cell treatment
with IL- 4 decreased c-fos/c-jun expression, CD23 MoAb reinduced
c-fos/c-jun and promoted the expression of cell maturation-associated
proto-oncogenes junB and c-fms, during the first 24 hours. Both IL-4 and
CD23 MoAb downregulated the expression of c-myb. CD23 ligation also induced
the production of TNF alpha by U937 cells. Inhibitors of cAMP and nitric
oxide reversed CD23-mediated modification in U937 cells. These data
evidence the ability of CD23 surface antigen to mediate terminal
differentiation of early leukemic myelomonocytic cells.
Volume 84,
Issue 9,
pp. 3095-3104,
11/01/1994
Copyright © 1994 by The American Society of Hematology

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