Abstract | PURPOSE: 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.
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Authors | Yan-Hua Xiao, Xin-Hui Li, Tan Tan, Ting Liang, Hong Yi, Mao-Yu Li, Gu-Qing Zeng, Xun-Xun Wan, Jia-Quan Qu, Qiu-Yan He, Jian-Huang Li, Yu Chen, Zhi-Qiang Xiao |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 137
Issue 12
Pg. 1831-40
(Dec 2011)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 21922325
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GLIPR1 protein, human
- Membrane Proteins
- Neoplasm Proteins
- Nerve Tissue Proteins
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Topics |
- Adolescent
- Adult
- Aged
- Cell Line, Tumor
- DNA Methylation
- Female
- Gene Silencing
- Genes, Tumor Suppressor
- Humans
- Leukemia, Myeloid, Acute
(genetics)
- Male
- Membrane Proteins
- Middle Aged
- Neoplasm Proteins
(genetics)
- Nerve Tissue Proteins
(genetics)
- Oligonucleotide Array Sequence Analysis
(methods)
- Promoter Regions, Genetic
- Reverse Transcriptase Polymerase Chain Reaction
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