Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an interferon (IFN)-induced molecule with apoptotic activity. We examined gene mutations in the death domains of TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), and in the TRAIL gene promoter in 46 chronic myelogenous leukemia (CML) patients. In 23 of the 46 patients, all the coding regions of TRAIL-R2 were also examined. However, no mutation or loss of heterozygosity was found. Furthermore, no mutation in the death domains of TRAIL-R1 and TRAIL-R2 genes, which causes amino acid change, was found in 18 myelodysplastic syndrome (MDS) patients. Ribonuclease protection assay (RPA) and real-time quantitative polymerase chain reaction using polymorphonuclear neutrophils of five new CML patients showed that the TRAIL mRNA expression was very low before in vitro IFN-α stimulation and markedly upregulated after IFN-α stimulation. FAS mRNA was also upregulated with IFN-α stimulation but the fold induction was far lower than that of TRAIL mRNA. In addition, RPA revealed that the ratio of (TRAIL-R1 plus TRAIL-R2) to TRAIL-R3 was also increased after IFN-α stimulation. Taken together, gene mutations of TRAIL-R1, TRAIL-R2 are infrequent in patients with CML and MDS. Andso is the TRAIL promoter for CML. These mutations seem unrelated to tumorigenesis, disease progression, and response to IFN-α therapy in CML. A markedly high induction of TRAIL mRNA by IFN-α may have some relevance to IFN-α action in CML patients.

Keywords:
Chronic myelogenous leukemia, Interferon, Mutation, Myelodysplastic syndrome, TRAIL
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2005
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