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Hypermethylation of death-associated protein (DAP) kinase CpG island is frequent not only in B-cell but also in T- and natural killer (NK)/T-cell malignancies

Authors
 Shin-ichi Nakatsuka  ;  Tetsuya Takakuwa  ;  Katsuyuki Aozasa  ;  Woo-Ick Yang  ;  Kazuhiro Nishii  ;  Motoko Yamaguchi  ;  Mieko Nishiu  ;  Yoshihiko Hoshida  ;  Yasuhiko Tomita 
Citation
 CANCER SCIENCE, Vol.94(1) : 87-91, 2003 
Journal Title
 CANCER SCIENCE 
ISSN
 1347-9032 
Issue Date
2003
MeSH
Antibodies, Monoclonal/pharmacology ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins ; Azacitidine/analogs & derivatives* ; Azacitidine/pharmacology ; B-Lymphocytes/enzymology ; Calcium-Calmodulin-Dependent Protein Kinases/biosynthesis ; Calcium-Calmodulin-Dependent Protein Kinases/genetics* ; CpG Islands* ; DNA Methylation*/drug effects ; Death-Associated Protein Kinases ; Decitabine ; Enzyme Induction ; Gene Expression Regulation, Neoplastic* ; Hematologic Neoplasms/enzymology ; Hematologic Neoplasms/genetics* ; Humans ; Jurkat Cells/drug effects ; Killer Cells, Natural/enzymology ; Leukemia-Lymphoma, Adult T-Cell/enzymology ; Leukemia-Lymphoma, Adult T-Cell/genetics ; Lymphoma, B-Cell/enzymology ; Lymphoma, B-Cell/genetics ; Lymphoma, T-Cell/enzymology ; Lymphoma, T-Cell/genetics ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics* ; Neoplastic Stem Cells/enzymology ; Promoter Regions, Genetic/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/enzymology ; fas Receptor/immunology
Keywords
12708480
Abstract
Death-associated protein (DAP) kinase is a pro-apoptotic serine/threonine kinase with a death domain, which is involved in apoptosis induced by interferon-gamma, tumor necrosis factor-alpha, and Fas ligand. Down-regulation of DAP kinase gene expression by hypermethylation of its promoter region might result in resistance to apoptotic cell death, and could provide a basis for tumor development. In the present study, we employed methylation-specific polymerase chain reaction to examine the methylation status of CpG islands in the DAP kinase gene in 19 cases of T-cell malignancies (including eight adult T-cell leukemia/lymphoma), 24 of natural killer (NK)/T-cell, and 34 of B-cell. Frequency of methylation was significantly higher in B-cell (27 of 34, 79.4%) than in T-cell malignancies (nine of 19, 47.4%) (P<0.05). Fifteen of 24 (62.5%) NK/T-cell lymphomas showed DNA methylation. One B-cell lymphoma cell line with DNA methylation was resistant to apoptotic stimuli, and treatment of the cells with a demethylating agent restored apoptotic cell death. These findings suggested that suppression of DAP kinase expression by DNA methylation might play a substantial role in the development of not only B-cell, but also T- and NK/T-cell lymphomas.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2003.tb01357.x/abstract
DOI
10.1111/j.1349-7006.2003.tb01357.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114396
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