Effect of interferon-alpha on the expression and release of the CD23 molecule in hairy cell leukemia.
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.
Genot
E
E
U.196 INSERM Recherche sur les interférons, Institut Curie, Paris, France.
Sarfati
M
M
Sigaux
F
F
Petit-Koskas
E
E
Billard
C
C
Mathiot
C
C
Falcoff
E
E
Delespesse
G
G
Kolb
J P
JP
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007158:Immunologic Techniques; D007167:Immunotherapy; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D011961:Receptors, Fc / Q000378:metabolism* / Q000502:physiology; D017455:Receptors, IgE; D011994:Recombinant Proteins; D012995:Solubility
D000944:Antigens, Differentiation, B-Lymphocyte; D007370:Interferon Type I; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4