RESUMEN
Objective To explore the expression of the mRNA level of Fas (CD95) ligand/FasL and Fas-associated phosphatase-1/FAP-1 in acute myeloid leukemia. Methods The expression of FasL and FAP-1 were detected in 54 patients with AML and 10 normal subjects by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). β-actin used as internal reference. The changes of FasL was observed after induction chemotherapy in 16 AML patients. The expression of Fas was detected in 54 patients with AML by flow cytometry. Results The mRNA levels of FasL and in 54 patients were remarkably higher(P 0.05). The mRNA levels of FAP-1 in 54 patients was remarkly higher than that of the normal control. 8/29 cases in Fas-positive group were positive for FAP-1 mRNA expression. 19/25 cases in the Fas-refractory group didn't express FAP-1 mRNA. Conclusion The expression of FasL was high in AML. The rates of complete remission were high in FasL positive cases. The FasL level declined in patients with good response to therapy. The expression of FAP-1was partly expressed in AML. The expression of FAP-1 was less in Fas positive group.
RESUMEN
Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.