{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:26:19Z","timestamp":1791566779448,"version":"4.3.4"},"reference-count":58,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Adult T-cell leukemia\/lymphoma (ATL) is a malignancy of mature CD4+ T cells caused by human T-cell lymphotropic virus type 1 (HTLV-1)\u2013induced T-cell transformation. After infection with HTLV-1, it takes several decades for HTLV-1 carriers to develop ATL. The prognosis of ATL remains poor despite several new agents being approved in the last few years. Recently, it has been noted that epigenetic abnormalities, both DNA methylation and trimethylation at histone H3Lys27 (H3K27me3), contribute to ATL leukemogenesis. Here, we investigated the effect of combination treatment with DNA demethylating agents (azacitidine [AZA], decitabine (DAC), and OR-2100 (OR21), which is a silylated derivative of DAC) and inhibitors of enhancer of zeste homolog 2 (EZH2) (EPZ-6438 and DS-3201b), which catalyze trimethylation of H3K27, in ATL. The combination of DAC and OR21 but not AZA with EZH inhibitors exhibited synergistic anti-ATL effects in\u00a0vitro and in\u00a0vivo, concomitant with DNA demethylation and reduction of H3K27me3. The combination induced gene expression reprogramming. Dual-specificity phosphatase 5 (DUSP5), an extracellular signal-regulated kinase (ERK)\u2013specific phosphatase, was identified as a key molecule that mediated the inhibitory effect of combination treatment by inactivating the ERK signaling pathway. DUSP5 was downregulated by DNA methylation and H3K27me3 accumulation in the promoter region in HTLV-1\u2013infected cells from patients with ATL during ATL leukemogenesis. The present results demonstrate that dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth by restoring DUSP5, and that dual targeting of aberrant DNA and histone methylation is a feasible therapeutic approach for ATL.<\/jats:p>","DOI":"10.1182\/bloodadvances.2022008362","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T18:18:18Z","timestamp":1671041898000},"page":"1545-1559","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":16,"title":["Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL"],"prefix":"10.1182","volume":"7","author":[{"given":"Yuki","family":"Kurahashi","sequence":"first","affiliation":[{"name":"1Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan"},{"name":"2OHARA Pharmaceutical Co., Ltd., Shiga, 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Medicine, Faculty of Medicine, Saga University, Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuharu","family":"Kamachi","sequence":"additional","affiliation":[{"name":"1Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan"},{"name":"3Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8375-3662","authenticated-orcid":false,"given":"Nao","family":"Yoshida-Sakai","sequence":"additional","affiliation":[{"name":"1Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Fukuda-Kurahashi","sequence":"additional","affiliation":[{"name":"1Department of Drug Discovery and Biomedical Sciences, Faculty of 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An open-label, single-arm, phase 2 trial of valemetostat in relapsed or refractory adult T-cell leukemia\/lymphoma. Blood. Published online 23 September 2022. https:\/\/doi.org\/10.1182\/blood.2022016862.","DOI":"10.1182\/blood.2022016862"},{"issue":"4","key":"2023042114594608200_bib23","first-page":"1043","article-title":"Increasing methylation of the CDKN2A gene is associated with the progression of adult T-cell leukemia","volume":"60","author":"Nosaka","year":"2000","journal-title":"Cancer Res"},{"issue":"7","key":"2023042114594608200_bib24","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1182\/blood.2019003084","article-title":"Targeting aberrant DNA hypermethylation as a driver of ATL leukemogenesis by using the new oral demethylating agent OR-2100","volume":"136","author":"Watanabe","year":"2020","journal-title":"Blood"},{"issue":"8","key":"2023042114594608200_bib25","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1158\/1535-7163.MCT-20-1125","article-title":"Silylation of deoxynucleotide analog yields an orally available drug with antileukemia 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