{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:49:32Z","timestamp":1783417772626,"version":"3.54.6"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Adenosine to inosine (A-to-I) RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes ADAR1 and ADAR2, has been shown to contribute to multiple cancers. However, other than chronic myeloid leukemia (CML) blast crisis, relatively little is known about its role in other types of hematological malignancies. Here, we found that ADAR2, but not ADAR1 and ADAR3, was specifically downregulated in the core binding factor (CBF) AML with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was repressed by the RUNX1-ETO AE9a fusion protein in a dominant negative manner. Further functional studies confirmed that ADAR2 could suppress leukemogenesis specifically in t(8;21) and inv16 AML cells dependent on its RNA editing capability. Expression of two exemplary ADAR2-regulated RNA editing targets COPA and COG3 inhibited clonogenic growth of human t(8;21) AML cells. Our findings support a hitherto unappreciated mechanism leading to ADAR2 dysregulation in CBF AML and highlight the functional relevance of loss of ADAR2-mediated RNA editing to CBF AML.<\/jats:p>","DOI":"10.1182\/blood.2022015830","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T21:16:51Z","timestamp":1676582211000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":6,"title":["Core binding factor fusion downregulation of ADAR2 RNA editing contributes to AML leukemogenesis"],"prefix":"10.1182","author":[{"given":"Mingrui","family":"Guo","sequence":"first","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hon Man Tim","family":"Chan","sequence":"additional","affiliation":[{"name":"National University Health System, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6639-8590","authenticated-orcid":false,"given":"Qi-Ling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Canecr Science Institute of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"An","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9316-2521","authenticated-orcid":false,"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-2706","authenticated-orcid":false,"given":"Yangyang","family":"Song","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Tongji University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi Hui","family":"Tan","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui En Vanessa","family":"Ng","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philomina Sona","family":"Peramangalam","sequence":"additional","affiliation":[{"name":"Blood Research Institute, Versiti, Milwaukee, WI, Wisconsin, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Qing","family":"Tan","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6794-0871","authenticated-orcid":false,"given":"Xinang","family":"Cao","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisaku","family":"Iwanaga","sequence":"additional","affiliation":[{"name":"Kumamoto University, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-754X","authenticated-orcid":false,"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Kumamoto Univerisity, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-0655","authenticated-orcid":false,"given":"Melissa G","family":"Ooi","sequence":"additional","affiliation":[{"name":"National University Cancer Institute Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-3362","authenticated-orcid":false,"given":"Wei Ying","family":"Jen","sequence":"additional","affiliation":[{"name":"National University Cancer Institute, Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang Piu","family":"Koh","sequence":"additional","affiliation":[{"name":"National University Health System, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Chan","sequence":"additional","affiliation":[{"name":"National University Hospital Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lip Kun","family":"Tan","sequence":"additional","affiliation":[{"name":"National University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufen","family":"Goh","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of 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Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-8335","authenticated-orcid":false,"given":"Wee Joo","family":"Chng","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3982-9054","authenticated-orcid":false,"given":"Motomi","family":"Osato","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7995-6942","authenticated-orcid":false,"given":"John Anto","family":"Pulikkan","sequence":"additional","affiliation":[{"name":"Blood Research Institute, Versiti, milwaukee, Wisconsin, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Science Institute of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1987-3878","authenticated-orcid":false,"given":"Leilei","family":"Chen","sequence":"additional","affiliation":[{"name":"National University of Singapore, Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-3888","authenticated-orcid":false,"given":"Daniel G.","family":"Tenen","sequence":"additional","affiliation":[{"name":"National University of Singapore, 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