Core binding factor fusion downregulation of ADAR2 RNA editing contributes to AML leukemogenesis
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- Mingrui Guo
- Cancer Science Institute of Singapore, Singapore, Singapore
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- Hon Man Tim Chan
- National University Health System, Singapore
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- Qi-Ling Zhou
- Canecr Science Institute of Singapore, Singapore, Singapore
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- Omer An
- Cancer Science Institute of Singapore, Singapore
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- Ying Li
- National University of Singapore, Singapore, Singapore
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- Yangyang Song
- School of Life Science and Technology, Tongji University, China
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- Zi Hui Tan
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
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- Hui En Vanessa Ng
- Cancer Science Institute of Singapore, Singapore, Singapore
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- Philomina Sona Peramangalam
- Blood Research Institute, Versiti, Milwaukee, WI, Wisconsin, United States
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- Zhi Qing Tan
- Cancer Science Institute of Singapore, Singapore, Singapore
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- Xinang Cao
- Cancer Science Institute of Singapore, Singapore
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- Eisaku Iwanaga
- Kumamoto University, Kumamoto, Japan
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- Masao Matsuoka
- Kumamoto Univerisity, Kumamoto, Japan
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- Melissa G Ooi
- National University Cancer Institute Singapore, Singapore, Singapore
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- Wei Ying Jen
- National University Cancer Institute, Singapore, Singapore, Singapore
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- Liang Piu Koh
- National University Health System, Singapore, Singapore
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- Esther Chan
- National University Hospital Singapore
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- Lip Kun Tan
- National University Hospital
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- Yufen Goh
- Cancer Science Institute of Singapore, Singapore, Singapore
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- Wilson Wang
- National University Health System, Singapore, Singapore
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- Bryan T.H. Koh
- National University Health System, Singapore, Singapore
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- Ming Chun Chan
- National University Health System, Singapore
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- Melissa J. Fullwood
- School of Biological Sciences, Nanyang Technological University, Singapore
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- Wee Joo Chng
- Cancer Science Institute of Singapore, Singapore
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- Motomi Osato
- Cancer Science Institute of Singapore, Singapore
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- John Anto Pulikkan
- Blood Research Institute, Versiti, milwaukee, Wisconsin, United States
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- Henry Yang
- Cancer Science Institute of Singapore, Singapore
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- Leilei Chen
- National University of Singapore, Singapore, Singapore
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- Daniel G. Tenen
- National University of Singapore, Singapore
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>
Journal
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- Blood
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Blood 2023-02-16
American Society of Hematology
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Keywords
Details 詳細情報について
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- CRID
- 1360580232157610752
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- ISSN
- 15280020
- 00064971
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- Data Source
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- Crossref
- KAKEN