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A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis
DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;2...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577530/ https://www.ncbi.nlm.nih.gov/pubmed/28539478 http://dx.doi.org/10.15252/emmm.201607180 |
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author | Li, Yonghui Ning, Qiaoyang Shi, Jinlong Chen, Yang Jiang, Mengmeng Gao, Li Huang, Wenrong Jing, Yu Huang, Sai Liu, Anqi Hu, Zhirui Liu, Daihong Wang, Lili Nervi, Clara Dai, Yun Zhang, Michael Q Yu, Li |
author_facet | Li, Yonghui Ning, Qiaoyang Shi, Jinlong Chen, Yang Jiang, Mengmeng Gao, Li Huang, Wenrong Jing, Yu Huang, Sai Liu, Anqi Hu, Zhirui Liu, Daihong Wang, Lili Nervi, Clara Dai, Yun Zhang, Michael Q Yu, Li |
author_sort | Li, Yonghui |
collection | PubMed |
description | DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(−) AMLs. This study demonstrated that a novel hypermethylated zinc finger‐containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1‐ETO at the transcriptional level in t(8;21) AML. Our findings also show that THAP10 is a bona fide target of miR‐383 that can be epigenetically activated by the AML1‐ETO recruiting co‐activator p300. In this study, we demonstrated that epigenetic suppression of THAP10 is the mechanistic link between AML1‐ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein that inhibits myeloid proliferation and promotes differentiation both in vitro and in vivo. Altogether, our results revealed an unexpected and important epigenetic mini‐circuit of AML1‐ETO/THAP10/miR‐383 in t(8;21) AML, in which epigenetic suppression of THAP10 predicts a poor clinical outcome and represents a novel therapeutic target. |
format | Online Article Text |
id | pubmed-5577530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55775302017-09-05 A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis Li, Yonghui Ning, Qiaoyang Shi, Jinlong Chen, Yang Jiang, Mengmeng Gao, Li Huang, Wenrong Jing, Yu Huang, Sai Liu, Anqi Hu, Zhirui Liu, Daihong Wang, Lili Nervi, Clara Dai, Yun Zhang, Michael Q Yu, Li EMBO Mol Med Research Articles DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(−) AMLs. This study demonstrated that a novel hypermethylated zinc finger‐containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1‐ETO at the transcriptional level in t(8;21) AML. Our findings also show that THAP10 is a bona fide target of miR‐383 that can be epigenetically activated by the AML1‐ETO recruiting co‐activator p300. In this study, we demonstrated that epigenetic suppression of THAP10 is the mechanistic link between AML1‐ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein that inhibits myeloid proliferation and promotes differentiation both in vitro and in vivo. Altogether, our results revealed an unexpected and important epigenetic mini‐circuit of AML1‐ETO/THAP10/miR‐383 in t(8;21) AML, in which epigenetic suppression of THAP10 predicts a poor clinical outcome and represents a novel therapeutic target. John Wiley and Sons Inc. 2017-05-24 2017-07 /pmc/articles/PMC5577530/ /pubmed/28539478 http://dx.doi.org/10.15252/emmm.201607180 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Li, Yonghui Ning, Qiaoyang Shi, Jinlong Chen, Yang Jiang, Mengmeng Gao, Li Huang, Wenrong Jing, Yu Huang, Sai Liu, Anqi Hu, Zhirui Liu, Daihong Wang, Lili Nervi, Clara Dai, Yun Zhang, Michael Q Yu, Li A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
title | A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
title_full | A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
title_fullStr | A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
title_full_unstemmed | A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
title_short | A novel epigenetic AML1‐ETO/THAP10/miR‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
title_sort | novel epigenetic aml1‐eto/thap10/mir‐383 mini‐circuitry contributes to t(8;21) leukaemogenesis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577530/ https://www.ncbi.nlm.nih.gov/pubmed/28539478 http://dx.doi.org/10.15252/emmm.201607180 |
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