{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:01:45Z","timestamp":1760144505667,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI Grant-in-Aid for Scientific Research (C)","doi-asserted-by":"publisher","award":["21K06703","24K18567"],"award-info":[{"award-number":["21K06703","24K18567"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI Grant-in-Aid for Early-Career Scientists","award":["21K06703","24K18567"],"award-info":[{"award-number":["21K06703","24K18567"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>5-azacytidine (AZA), a representative DNA-demethylating drug, has been widely used to treat myelodysplastic syndromes (MDS). However, it remains unclear whether AZA\u2019s DNA demethylation of any specific gene is correlated with clinical responses to AZA. In this study, we investigated genes that could contribute to the development of evidence-based epigenetic therapeutics with AZA. A DNA microarray identified that AZA specifically upregulated the expression of 438 genes in AZA-sensitive MDS-L cells but not in AZA-resistant counterpart MDS-L\/CDA cells. Of these 438 genes, the ALOX12 gene was hypermethylated in MDS-L cells but not in MDS-L\/CDA cells. In addition, we further found that (1) the ALOX12 gene was hypermethylated in patients with MDS compared to healthy controls; (2) MDS classes with excess blasts showed a relatively lower expression of ALOX12 than other classes; (3) a lower expression of ALOX12 correlated with higher bone marrow blasts and a shorter survival in patients with MDS; and (4) an increased ALOX12 expression after AZA treatment was associated with a favorable response to AZA treatment. Taking these factors together, an enhanced expression of the ALOX12 gene may predict favorable therapeutic responses to AZA therapy in MDS.<\/jats:p>","DOI":"10.3390\/ijms25094583","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T05:28:06Z","timestamp":1713850086000},"page":"4583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced ALOX12 Gene Expression Predicts Therapeutic Susceptibility to 5-Azacytidine in Patients with Myelodysplastic Syndromes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5301-1481","authenticated-orcid":false,"given":"Taichi","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Basic Medical Research Unit, St. Mary\u2019s Research Center, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Basic Medical Research Unit, St. Mary\u2019s Research Center, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nao","family":"Yoshida-Sakai","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Mary\u2019s Hospital, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Katsuchi","sequence":"additional","affiliation":[{"name":"Basic Medical Research Unit, St. Mary\u2019s Research Center, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuon","family":"Kanazawa","sequence":"additional","affiliation":[{"name":"Basic Medical Research Unit, St. Mary\u2019s Research Center, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Okamura","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Mary\u2019s Hospital, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Hematology, St. Mary\u2019s Hospital, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Ono","sequence":"additional","affiliation":[{"name":"Basic Medical Research Unit, St. Mary\u2019s Research Center, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihiko","family":"Kuwano","sequence":"additional","affiliation":[{"name":"Basic Medical Research Unit, St. Mary\u2019s Research Center, 422, Tsubuku-Honmachi, Kurume 850-8543, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1200\/JCO.2009.23.4781","article-title":"DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes","volume":"28","author":"Shen","year":"2010","journal-title":"J. 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