PURPOSE: To identify methylation-silenced genes in acute myeloid leukemia (AML). METHODS: Microarray analyses were performed in AML cell line HL-60 cells exposed to the demethylating agent 5-aza-2dC. The methylation status and expression of glioma pathogenesis-related protein 1 (GLIPR1), one of highly induced genes by demethylation, were further detected in six hematopoietic malignancy cell lines and 260 bone marrow samples from leukemia patients and nonmalignant diseases as control, as well as pre-treated and post-treated bone marrow samples from 24 complete remission AML patients received chemotherapy using MS-PCR, bisulfite DNA sequencing, RT-PCR, and Western blotting. RESULTS: One hundred and nine genes were significantly induced by demethylation in HL-60 cells, 12 genes of which were confirmed by RT-PCR. GLIPR1, a tumor suppressor gene, was frequently methylation-silenced in AML cell lines and AML patients, but not in the other hematopoietic malignancy cell lines and patients. The frequencies of methylation-silenced GLIPR1 in the pre-treatment were significantly higher than those in the post-treatment in complete remission AML patients. CONCLUSION: We identify 109 genes induced by demethylation in HL-60 cells, and demonstrate that GLIPR1 is a methylation-silenced gene in the AML patients, and may serve as a marker for monitoring disease activity during therapy in the AML patients. The data provide the important information for studying the pathogenesis of AML and discovering the target genes of methylating agents.
PURPOSE: To identify methylation-silenced genes in acute myeloid leukemia (AML). METHODS: Microarray analyses were performed in AML cell line HL-60 cells exposed to the demethylating agent 5-aza-2dC. The methylation status and expression of glioma pathogenesis-related protein 1 (GLIPR1), one of highly induced genes by demethylation, were further detected in six hematopoietic malignancy cell lines and 260 bone marrow samples from leukemiapatients and nonmalignant diseases as control, as well as pre-treated and post-treated bone marrow samples from 24 complete remission AMLpatients received chemotherapy using MS-PCR, bisulfite DNA sequencing, RT-PCR, and Western blotting. RESULTS: One hundred and nine genes were significantly induced by demethylation in HL-60 cells, 12 genes of which were confirmed by RT-PCR. GLIPR1, a tumor suppressor gene, was frequently methylation-silenced in AML cell lines and AMLpatients, but not in the other hematopoietic malignancy cell lines and patients. The frequencies of methylation-silenced GLIPR1 in the pre-treatment were significantly higher than those in the post-treatment in complete remission AMLpatients. CONCLUSION: We identify 109 genes induced by demethylation in HL-60 cells, and demonstrate that GLIPR1 is a methylation-silenced gene in the AMLpatients, and may serve as a marker for monitoring disease activity during therapy in the AMLpatients. The data provide the important information for studying the pathogenesis of AML and discovering the target genes of methylating agents.
Authors: K Naruishi; T L Timme; N Kusaka; T Fujita; G Yang; A Goltsov; T Satoh; X Ji; W Tian; E Abdelfattah; T Men; M Watanabe; K Tabata; T C Thompson Journal: Cancer Gene Ther Date: 2006-02-17 Impact factor: 5.987
Authors: Gretchen Johnston; Haley E Ramsey; Qi Liu; Jing Wang; Kristy R Stengel; Shilpa Sampathi; Pankaj Acharya; Maria Arrate; Matthew C Stubbs; Timothy Burn; Michael R Savona; Scott W Hiebert Journal: Gene Date: 2020-05-15 Impact factor: 3.688