{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:33:59Z","timestamp":1767598439055,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HK inno. N.","award":["CS2018_0009"],"award-info":[{"award-number":["CS2018_0009"]}]},{"DOI":"10.13039\/501100002560","name":"Soonchunhyang University","doi-asserted-by":"publisher","award":["10210023"],"award-info":[{"award-number":["10210023"]}],"id":[{"id":"10.13039\/501100002560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = \u22120.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.<\/jats:p>","DOI":"10.3390\/cimb43020065","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:35:32Z","timestamp":1628156132000},"page":"917-931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["TET2 Mutation and High miR-22 Expression as Biomarkers to Predict Clinical Outcome in Myelodysplastic Syndrome Patients Treated with Hypomethylating Therapy"],"prefix":"10.3390","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5897-8309","authenticated-orcid":false,"given":"Jina","family":"Yun","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-2210","authenticated-orcid":false,"given":"Young Sok","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geum Ha","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hee","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-9950","authenticated-orcid":false,"given":"Chan Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Byung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Chungcheongnam-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Ho","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hemato-Oncology, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si 14584, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.5045\/br.2014.49.4.216","article-title":"Pathogenesis of myelodysplastic syndromes: An overview of molecular and non-molecular aspects of the disease","volume":"49","author":"Visconte","year":"2014","journal-title":"Blood Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.5045\/br.2015.50.4.204","article-title":"Nationwide statistical analysis of myeloid malignancies in Korea: Incidence and survival rate from 1999 to 2012","volume":"50","author":"Park","year":"2015","journal-title":"Blood Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1182\/blood-2018-10-844621","article-title":"Genetics of MDS","volume":"133","author":"Ogawa","year":"2019","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/leu.2013.343","article-title":"Epigenetics of myelodysplastic syndromes","volume":"28","author":"Itzykson","year":"2014","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/imr.12246","article-title":"The role of mutations in epigenetic regulators in myeloid malignancies","volume":"263","author":"Woods","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1182\/blood-2018-03-785915","article-title":"How I treat MDS after hypomethylating agent failure","volume":"133","author":"Santini","year":"2019","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.5045\/br.2013.48.2.87","article-title":"Use of azacitidine for myelodysplastic syndromes: Controversial issues and practical recommendations","volume":"48","author":"Kim","year":"2013","journal-title":"Blood Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.leukres.2016.08.012","article-title":"Biomarkers of angiogenesis as prognostic factors in myelodysplastic syndrome patients treated with hypomethylating agents","volume":"50","author":"Kim","year":"2016","journal-title":"Leuk. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1101\/gad.276568.115","article-title":"Role of TET enzymes in DNA methylation, development, and cancer","volume":"30","author":"Rasmussen","year":"2016","journal-title":"Genes Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1101\/gad.260174.115","article-title":"Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis","volume":"29","author":"Rasmussen","year":"2015","journal-title":"Genes Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1158\/0008-5472.CAN-14-0739","article-title":"TET2 mutations affect Non-CpG island DNA methylation at enhancers and transcription factor-binding sites in chronic myelomonocytic Leukemia","volume":"75","author":"Yamazaki","year":"2015","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.celrep.2013.08.050","article-title":"An Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant Hematopoiesis","volume":"5","author":"Cheng","year":"2013","journal-title":"Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.stem.2013.06.003","article-title":"The Oncogenic MicroRNA miR-22 Targets the TET2 Tumor Suppressor to Promote Hematopoietic Stem Cell Self-Renewal and Transformation","volume":"13","author":"Song","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/leu.2011.71","article-title":"Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias","volume":"25","author":"Itzykson","year":"2011","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1182\/blood-2014-06-582809","article-title":"TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients","volume":"124","author":"Bejar","year":"2014","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1182\/blood-2009-03-209262","article-title":"The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes","volume":"114","author":"Vardiman","year":"2009","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1182\/blood.V89.6.2079","article-title":"International scoring system for evaluating prognosis in myelodysplastic syndromes","volume":"89","author":"Greenberg","year":"1997","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1182\/blood-2012-03-420489","article-title":"Revised international prognostic scoring system for myelodysplastic syndromes","volume":"120","author":"Greenberg","year":"2012","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1182\/blood-2005-10-4149","article-title":"Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia","volume":"108","author":"Cheson","year":"2006","journal-title":"Blood"},{"key":"ref_20","unstructured":"(2020, September 11). Myelodysplastic Syndromes. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology-V1.2021, National Comprehensive Cancer Network. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/mds.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41408-018-0074-7","article-title":"Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome","volume":"8","author":"Hou","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3824","DOI":"10.1182\/blood-2011-05-352039","article-title":"Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: A phase 2 trial","volume":"118","author":"Braun","year":"2011","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/leu.2013.269","article-title":"Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms","volume":"28","author":"Traina","year":"2014","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55264","DOI":"10.18632\/oncotarget.10526","article-title":"Somatic mutations predict outcomes of hypomethylating therapy in patients with myelodysplastic syndrome","volume":"7","author":"Jung","year":"2016","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1182\/bloodadvances.2019000192","article-title":"DNA methylation identifies genetically and prognostically distinct subtypes of myelodysplastic syndromes","volume":"3","author":"Reilly","year":"2019","journal-title":"Blood Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1182\/blood-2010-03-274704","article-title":"Next-generation sequencing of the TET2 gene in 355 MDS and CMMLpatients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value","volume":"116","author":"Smith","year":"2010","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1182\/blood-2017-05-783050","article-title":"Gene expression and risk of leukemic transformation in myelodysplasia","volume":"130","author":"Shiozawa","year":"2017","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nature09586","article-title":"Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2","volume":"468","author":"Ko","year":"2010","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1182\/blood-2010-12-325241","article-title":"Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies","volume":"118","author":"Li","year":"2011","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e351","DOI":"10.3324\/haematol.2015.126227","article-title":"Adverse prognostic effect of homozygous TET2 mutation on the relapse risk of acute myeloid leukaemia in patients of normal karyotype","volume":"100","author":"Ahn","year":"2015","journal-title":"Haematologica"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/43\/2\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:41:03Z","timestamp":1760164863000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/43\/2\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,5]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cimb43020065"],"URL":"https:\/\/doi.org\/10.3390\/cimb43020065","relation":{},"ISSN":["1467-3045"],"issn-type":[{"type":"electronic","value":"1467-3045"}],"subject":[],"published":{"date-parts":[[2021,8,5]]}}}