{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:15:28Z","timestamp":1784661328494,"version":"3.55.0"},"reference-count":72,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T00:00:00Z","timestamp":1551225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1D1A1A02937071"],"award-info":[{"award-number":["2016R1D1A1A02937071"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A6A1A03023718"],"award-info":[{"award-number":["2018R1A6A1A03023718"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Follicular lymphoma (FL) is the most common indolent B\u2010cell non\u2010Hodgkin lymphoma (NHL) with genetic alterations of BCL\u20102, KMT2B, and KMT6. FL is refractory to conventional chemotherapy and is still incurable in most patients. Thus, new drugs and\/or novel combination treatment strategies are needed to further improve FL patient outcome. We investigated the efficacy of the histone deacetylase 6 (HDAC6) inhibitor A452 combined with a Bruton's tyrosine kinase (BTK) inhibitor ibrutinib on NHL and the underlying mechanisms compared with the current clinically tested HDAC6 inhibitor ACY\u20101215. We first showed that FL is the most sensitive to HDAC6 inhibitor. We showed that combining A452 with ibrutinib led to the synergistic inhibition of cell growth and decreased viability of FL cells, as well as increased levels of apoptosis. Similar synergistic interactions occur in chronic lymphocytic leukemia (CLL) and germinal center diffuse large B\u2010cell lymphoma cells (DLBCL). Enhanced cell death is associated with AKT and ERK1\/2 inactivation and increased DNA damage (induction of \u03b3H2A.X and reduction of pChk1\/2). In addition, A452 downregulates c\u2010Myc, an effect significantly enhanced by ibruninib. Although ACY\u20101215 is less potent than A452, it displays synergism with ibrutinib. Overall, our results suggest that A452 is more effective as an anticancer agent than ACY\u20101215 in FL. These findings suggest that a combination of HDAC6\u2010selective inhibitor and ibrutinib is a potent therapeutic strategy for NHL including FL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22983","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T18:30:08Z","timestamp":1548786608000},"page":"944-956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The HDAC6\u2010selective inhibitor is effective against non\u2010Hodgkin lymphoma and synergizes with ibrutinib in follicular lymphoma"],"prefix":"10.1002","volume":"58","author":[{"given":"Dong Hoon","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy Yonsei Institute of Pharmaceutical Sciences Yonsei University Incheon Republic of Korea"},{"name":"Department of Integrated OMICS for Biomedical Science Yonsei University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Go Woon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy Yonsei Institute of Pharmaceutical Sciences Yonsei University Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-4415","authenticated-orcid":false,"given":"So Hee","family":"Kwon","sequence":"additional","affiliation":[{"name":"College of Pharmacy Yonsei Institute of Pharmaceutical Sciences Yonsei University Incheon Republic of Korea"},{"name":"Department of Integrated OMICS for Biomedical Science Yonsei University Seoul Republic of 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