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TET2, a DNA dioxygenase, requires 2-oxoglutarate and Fe(II) to oxidize 5-methylcytosine. <jats:italic>TET2<\/jats:italic><jats:sup><jats:italic>MT<\/jats:italic><\/jats:sup> thus result in hypermethylation and transcriptional repression. Ascorbic acid (AA) increases dioxygenase activity by facilitating Fe(III)\/Fe(II) redox reaction and may alleviate some biological consequences of <jats:italic>TET2<\/jats:italic><jats:sup><jats:italic>MT<\/jats:italic><\/jats:sup> by restoring dioxygenase activity. Here, we report the utility of AA in the prevention of <jats:italic>TET2<\/jats:italic><jats:sup><jats:italic>MT<\/jats:italic><\/jats:sup> myeloid neoplasia (MN), clarify the mechanistic underpinning of the TET2-AA interactions, and demonstrate that the ability of AA to restore TET2 activity in cells depends on N- and C-terminal lysine acetylation and nature of <jats:italic>TET2<\/jats:italic><jats:sup><jats:italic>MT<\/jats:italic><\/jats:sup>. Consequently, pharmacologic modulation of acetyltransferases and histone deacetylases may regulate TET dioxygenase-dependent AA effects. Thus, our study highlights the contribution of factors that may enhance or attenuate AA effects on TET2 and provides a rationale for novel therapeutic approaches including combinations of AA with class I\/II HDAC inhibitor or sirtuin activators in <jats:italic>TET2<\/jats:italic><jats:sup><jats:italic>MT<\/jats:italic><\/jats:sup> leukemia.<\/jats:p>","DOI":"10.1038\/s42003-020-01220-9","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T10:02:52Z","timestamp":1599472972000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Context dependent effects of ascorbic acid treatment in TET2 mutant myeloid neoplasia"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8002-5141","authenticated-orcid":false,"given":"Yihong","family":"Guan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward F.","family":"Greenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metis","family":"Hasipek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra M.","family":"Kerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-1511","authenticated-orcid":false,"given":"Daniel","family":"Gackowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Zarakowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9701-1851","authenticated-orcid":false,"given":"Tomas","family":"Radivoyevitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Willard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Visconte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-8578","authenticated-orcid":false,"given":"Hideki","family":"Makishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Nazha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mridul","family":"Mukherji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkael A.","family":"Sekeres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-1031","authenticated-orcid":false,"given":"Yogen","family":"Saunthararajah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Oli\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw P.","family":"Maciejewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-5255","authenticated-orcid":false,"given":"Babal K.","family":"Jha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,7]]},"reference":[{"key":"1220_CR1","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1038\/s41375-018-0150-9","volume":"32","author":"CM Hirsch","year":"2018","unstructured":"Hirsch, C. 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