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論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	A novel non-invasive monitoring assay of 5-azacitidine efficacy using global DNA methylation of peripheral blood in myelodysplastic syndrome.
掲載誌名	正式名：Drug design, development and therapy 略　 称：Drug Des Devel Ther ISSNコード：(1177-8881)1177-8881(Linking)
巻・号・頁	13,pp.1821-1833
著者・共著者	Asano Michiyo, Ohyashiki Junko H, Kobayashi-Kawana Chiaki, Umezu Tomohiro, Imanishi Satoshi, Azuma Kenko, Akahane Daigo, Fujimoto Hiroaki, Ito Yoshikazu, Ohyashiki Kazuma
発行年月	2019
概要	Purpose: Monitoring response and resistance to 5-azacitidine (AZA) is essential when treating patients with myelodysplastic syndrome (MDS). To quantify methylated DNA not only in the promoter region but also in the gene body, we established a single-molecule methylation assay (SMMA). Patients and methods: We first investigated the methylation extent (expressed as methylation index [MI]) by SMMA among 28 MDS and 6 post-MDS acute myeloid leukemia patients. We then analyzed the MI in 13 AZA-treated patients. Results: Whole-blood DNA from all 34 patients had low MI values compared with healthy volunteers (P<0.0001). DNA hypomethylation in MDS patients was more evident in neutrophils (P=0.0008) than in peripheral mononuclear cells (P=0.0713). No consistent pattern of genome-wide DNA hypomethylation was found among MDS subtypes or revised International Prognostic Scoring System (IPSS-R) categories; however, we found that the MI was significantly increased for patients at very high risk who were separated by the new cytogenetic scoring system for IPSS-R (P=0.0398). There was no significant difference in MI before AZA, regardless of the response to AZA (P=0.8689); however, sequential measurement of MI in peripheral blood demonstrated that AZA non-responders did not have normalized MI at the time of next course of AZA (P=0.0352). Conclusion: Our results suggest that sequential SMMA of peripheral blood after AZA may represent a non-invasive monitoring marker for AZA efficacy in MDS patients.
DOI	10.2147/DDDT.S195071
PMID	31239639