Fas-Mediated Modulation of Bcr/Abl in Chronic Myelogenous Leukemia Results in Differential Effects on Apoptosis

摘要: Fas-R is expressed constitutively in CD34(+) cells of patients with chronic myelogenous leukemia (CML); triggering results decreased proliferation rate due to apoptosis clonogenic cells. We have already shown that alpha-interferon (IFN-alpha) enhances expression on CML progenitor cells, thus increasing their sensitivity agonists. Although it appears IFN-alpha can prime for the effects Fas, response vivo not a constant feature patients. studied mechanisms Fas-mediated 11 suffering from phase and tried see whether there was correlation between vitro inducibility after clinical IFN-alpha. After priming IFN-alpha, Fas resulted suppression hematopoietic cell growth seven eight who had optimal hematologic IFN-alpha; same conditions, no inhibitory agonist observed three proved be poor responders In induced dose-dependent cells; this effect associated decrease bcr/abl protein level. derived culture remained unchanged presence downmodulation observed. Finally, we measured mRNA by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) found amounts specific mRNA, finding which consistent posttranscriptional regulation expression. It p210 restores susceptibility addition, studies may predict treatment.