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Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia

The AML1-ETO fusion protein (A/E), which results from the t(8;21) translocation, is considered to be a leukemia-initiating event. Identifying the mechanisms underlying the oncogenic activity of A/E remains a major challenge. In this study, we identified a specific down-regulation of brain acid-solub...

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Autores principales: Zhou, Lei, Fu, Lin, Lv, Na, Liu, Jing, Li, Yan, Chen, Xiaosu, Xu, Qingyu, Chen, Guofeng, Pang, Baoxu, Wang, Lili, Li, Yonghui, Zhang, Xiaodong, Yu, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938046/
https://www.ncbi.nlm.nih.gov/pubmed/29674693
http://dx.doi.org/10.1038/s12276-018-0067-4
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author Zhou, Lei
Fu, Lin
Lv, Na
Liu, Jing
Li, Yan
Chen, Xiaosu
Xu, Qingyu
Chen, Guofeng
Pang, Baoxu
Wang, Lili
Li, Yonghui
Zhang, Xiaodong
Yu, Li
author_facet Zhou, Lei
Fu, Lin
Lv, Na
Liu, Jing
Li, Yan
Chen, Xiaosu
Xu, Qingyu
Chen, Guofeng
Pang, Baoxu
Wang, Lili
Li, Yonghui
Zhang, Xiaodong
Yu, Li
author_sort Zhou, Lei
collection PubMed
description The AML1-ETO fusion protein (A/E), which results from the t(8;21) translocation, is considered to be a leukemia-initiating event. Identifying the mechanisms underlying the oncogenic activity of A/E remains a major challenge. In this study, we identified a specific down-regulation of brain acid-soluble protein 1 (BASP1) in t(8;21) acute myeloid leukemia (AML). A/E recognized AML1-binding sites and recruited DNA methyltransferase 3a (DNMT3a) to the BASP1 promoter sequence, which triggered DNA methylation-mediated silencing of BASP1. Ectopic expression of BASP1 inhibited proliferation and the colony-forming ability of A/E-positive AML cell lines and led to apoptosis and cell cycle arrest. The DNMT inhibitor decitabine up-regulated the expression of BASP1 in A/E-positive AML cell lines. In conclusion, our data suggest that BASP1 silencing via promoter methylation may be involved in A/E-mediated leukemogenesis and that BASP1 targeting may be an actionable therapeutic strategy in t(8;21) AML.
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spelling pubmed-59380462018-05-15 Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia Zhou, Lei Fu, Lin Lv, Na Liu, Jing Li, Yan Chen, Xiaosu Xu, Qingyu Chen, Guofeng Pang, Baoxu Wang, Lili Li, Yonghui Zhang, Xiaodong Yu, Li Exp Mol Med Article The AML1-ETO fusion protein (A/E), which results from the t(8;21) translocation, is considered to be a leukemia-initiating event. Identifying the mechanisms underlying the oncogenic activity of A/E remains a major challenge. In this study, we identified a specific down-regulation of brain acid-soluble protein 1 (BASP1) in t(8;21) acute myeloid leukemia (AML). A/E recognized AML1-binding sites and recruited DNA methyltransferase 3a (DNMT3a) to the BASP1 promoter sequence, which triggered DNA methylation-mediated silencing of BASP1. Ectopic expression of BASP1 inhibited proliferation and the colony-forming ability of A/E-positive AML cell lines and led to apoptosis and cell cycle arrest. The DNMT inhibitor decitabine up-regulated the expression of BASP1 in A/E-positive AML cell lines. In conclusion, our data suggest that BASP1 silencing via promoter methylation may be involved in A/E-mediated leukemogenesis and that BASP1 targeting may be an actionable therapeutic strategy in t(8;21) AML. Nature Publishing Group UK 2018-04-20 /pmc/articles/PMC5938046/ /pubmed/29674693 http://dx.doi.org/10.1038/s12276-018-0067-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.
spellingShingle Article
Zhou, Lei
Fu, Lin
Lv, Na
Liu, Jing
Li, Yan
Chen, Xiaosu
Xu, Qingyu
Chen, Guofeng
Pang, Baoxu
Wang, Lili
Li, Yonghui
Zhang, Xiaodong
Yu, Li
Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
title Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
title_full Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
title_fullStr Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
title_full_unstemmed Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
title_short Methylation-associated silencing of BASP1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
title_sort methylation-associated silencing of basp1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938046/
https://www.ncbi.nlm.nih.gov/pubmed/29674693
http://dx.doi.org/10.1038/s12276-018-0067-4
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