Involvement of Fas-Mediated Apoptosis in the Inhibitory Effects of Interferon-a in Chronic Myelogenous Leukemia

Interferon-a (IFN-a) is an established treatment for chronic marginal antiproliferative effects on both normal and CML BM progenitors. In contrast, a Fas-R agonist, the anti-CD95 myelogenous leukemia (CML) in chronic phase, but the mechanism of its antileukemic activity is not clear. One posmonoclonal antibody CH11, inhibited colony formation from normal progenitors, and the inhibition was even stronger sible mechanism of action might include the induction of apoptosis, and especially Fas-mediated cell killing may play on CML progenitors. When CML BM cells were cultured in the presence of IFN-a, Fas-R–mediated inhibition of colony an important role in the elimination of malignant cells. We investigated Fas receptor (Fas-R) expression and the consegrowth was potentiated in a dose-dependent fashion, consistent with IFN-a induction of Fas-R expression. This funcquences of Fas-R triggering in CML patients. Using two-color flow cytometry, we found a significantly higher number of tional effect did not require the presence of accessory cells, since similar results were obtained with purified CD34 cells. Fas-R–expressing CD34 cells in the bone marrow (BM) of CML patients compared with normal subjects. We have preIn suspension cultures, we demonstrated that suppression of CML hematopoiesis by IFN-a and Fas-R agonist was exviously shown that IFN-g induces Fas-R expression on CD34 cells; in this study, we investigated whether IFN-a induces erted through Fas-R–mediated induction of apoptosis. Our findings suggest that the Fas-R/Fas-ligand system might be Fas-R expression on CML progenitor cells. Dose-dependent induction of Fas-R expression was observed after IFN-a stiminvolved in the immunologic regulation of CML progenitor growth and that its effect can be amplified by IFN-a. ulation of CD34 cells from CML BM. In methylcellulose culture, IFN-a alone at a therapeutic concentration showed only q 1997 by The American Society of Hematology.