演題詳細

一般口演 / Oral Session

【E】一般口演 16 (Oral Session 16) :MDS:Clinical Research 3

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日程
2013年10月11日(金)
時間
10:00 - 11:30
会場
第14会場 / Room No.14 (札幌市教育文化会館 3F 研修室305)
座長・司会
石川 隆之 (Takayuki Ishikawa):1
1:Department of Hematology, Kobe City Medical Center General Hospital, Japan
 
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Clinical and experimental assessment of 5-azacytidine resistance in patients with MDS

演題番号 : OS-1-83

浅野 倫代 (Michiyo Asano):1、今西 哲 (Satoshi Imanishi):2、梅津 知宏 (Tomohiro Umezu):2,3、大屋敷 純子 (Junko Ohyashiki):2、大屋敷 一馬 (Kazuma Ohyashiki):1,3

1:Department of Hematology, Tokyo Medical University、2:Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University、3:Department of Molecular Science, Tokyo Medical University

 

Background and Aim:To clarify the molecular mechanism of 5-azacytidine (AZA), we performed sequential analysis of DNA methylation index (DMI) in AZA-treated pts, and molecular biological analysis using AZA-resistant cell lines.Method:After obtaining written informed consent, 15 MDS pts were enrolled in this study. Global methylation status of each specimen was assessed using a single molecule methylation assay, and then percentage of methylated DNA in the sample was expressed as DMI (0-100%). Two AZA-resistant cell lines (RU937, and RHL60) established in our laboratory were used for gene expression profiling, as well as experiments using specific inhibitors. Results and Discussion:DMI showed a distinct pattern in AZA-treated pts; DMI was reduced at day 7 after AZA administration, and restored at day 28 in responders. It was notable that restoration of DMI was not observed in AZA-resistant MDS pts. Gene expression profiling using RU937 and RHL60 revealed the involvement of pyrimidine metabolism pathway, and they re-acquired sensitivity to AZA in the presence of an inhibitor of CTP synthase, indicating that adaptation in pyrimidine metabolism, particularly the accelerated synthesis of CTP from UTP, may play an important role in the development of an AZA-resistant phenotype.Conclusion: Our results indicate that DMI pattern may be a predictive marker for AZA resistance in treating MDS pts, and AZA-resistant phenotype in part depended on the adaptation in pyrimidine metabolism.

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