Effect of interferon-alpha on the expression and release of the CD23
molecule in hairy cell leukemia
E Genot, M Sarfati, F Sigaux, E Petit-Koskas, C Billard, C Mathiot, E Falcoff, G Delespesse and JP Kolb
U.196 INSERM Recherche sur les interferons, Institut Curie, Paris, France.
Hairy cells are stimulated to DNA synthesis by low molecular weight B cell
growth factor (LMW-BCGF) and this proliferative response is suppressed by
interferon (IFN)-alpha, both in vitro and in vivo. The suggestion that the
CD23 molecule (Fc epsilon II receptor) might be involved in the signalling
pathway of LMW-BCGF prompted us to study the expression of this molecule on
hairy cells and its modulation by IFN- alpha. By flow cytometry and direct
binding experiments with anti CD23 monoclonal antibodies, the presence of
the CD23 antigen was detected in 7 of 12 cases tested, on variable
percentages of cells, ranging from low to medium expression. In vitro
incubation of hairy cells with IFN- alpha, which elicits a suppression of
the proliferative response of these cells to LMW-BCGF, induced a parallel
significant reduction of CD23 expression in only three cases. Similarly, a
transient in vivo decrease of CD23 expression, concommitant with an
inhibition of the LMW- BCGF response, could be detected in only one of
three patients injected with IFN-alpha. Soluble sCD23/IgE-binding factor
(BF) was quantitated in the serum from six other patients with
hyperleukocytic hairy cell leukemia (HCL) undergoing a clinical trial of
IFN-alpha therapy. Before treatment, these patients presented higher
concentrations of the cleaved soluble form of the CD23 molecule than normal
controls. Within a few weeks of IFN-alpha administration, these levels
markedly decreased, paralleling a diminution of blood leukemic cells. Of
interest, no such diminution was noticed for another patient resistant to
IFN-alpha therapy. These results show that the proliferative response of
hairy cells to LMW-BCGF is not linked to the expression of the CD23 marker.
Besides, when the latter molecule was present, its decrease following
IFN-alpha treatment, which could be detected in some cases, was not
necessarily required for the suppression of the LMW-BCGF response and is
thus not mandatory for the therapeutic efficacy of IFN- alpha. Our results
point out that quantitation of serum sCD23/IgE-BF, whether related to a
process of autocrine proliferation or not, is a parameter of potential
importance for therapy monitoring.
Volume 74,
Issue 7,
pp. 2455-2463,
11/15/1989
Copyright © 1989 by The American Society of Hematology
