Suppression of Transposable Elements in Leukemic Stem Cells

Abstract Genomic transposable elements (TEs) comprise nearly half of the human genome. The expression of TEs is considered potentially hazardous, as it can lead to insertional mutagenesis and genomic instability. However, recent studies have revealed that TEs are involved in immune-mediated cell cle...

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Autores principales:	Anthony R. Colombo, Asif Zubair, Devi Thiagarajan, Sergey Nuzhdin, Timothy J. Triche, Giridharan Ramsingh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bff7310f125740afb6584afd507b61a5
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spelling	oai:doaj.org-article:bff7310f125740afb6584afd507b61a52021-12-02T12:30:17ZSuppression of Transposable Elements in Leukemic Stem Cells10.1038/s41598-017-07356-92045-2322https://doaj.org/article/bff7310f125740afb6584afd507b61a52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07356-9https://doaj.org/toc/2045-2322Abstract Genomic transposable elements (TEs) comprise nearly half of the human genome. The expression of TEs is considered potentially hazardous, as it can lead to insertional mutagenesis and genomic instability. However, recent studies have revealed that TEs are involved in immune-mediated cell clearance. Hypomethylating agents can increase the expression of TEs in cancer cells, inducing ‘viral mimicry’, causing interferon signalling and cancer cell killing. To investigate the role of TEs in the pathogenesis of acute myeloid leukaemia (AML), we studied TE expression in several cell fractions of AML while tracking its development (pre-leukemic haematopoietic stem cells, leukemic stem cells [LSCs], and leukemic blasts). LSCs, which are resistant to chemotherapy and serve as reservoirs for relapse, showed significant suppression of TEs and interferon pathways. Similarly, high-risk cases of myelodysplastic syndrome (MDS) showed far greater suppression of TEs than low-risk cases. We propose TE suppression as a mechanism for immune escape in AML and MDS. Repression of TEs co-occurred with the upregulation of several genes known to modulate TE expression, such as RNA helicases and autophagy genes. Thus, we have identified potential pathways that can be targeted to activate cancer immunogenicity via TEs in AML and MDS.Anthony R. ColomboAsif ZubairDevi ThiagarajanSergey NuzhdinTimothy J. TricheGiridharan RamsinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anthony R. Colombo Asif Zubair Devi Thiagarajan Sergey Nuzhdin Timothy J. Triche Giridharan Ramsingh Suppression of Transposable Elements in Leukemic Stem Cells
description	Abstract Genomic transposable elements (TEs) comprise nearly half of the human genome. The expression of TEs is considered potentially hazardous, as it can lead to insertional mutagenesis and genomic instability. However, recent studies have revealed that TEs are involved in immune-mediated cell clearance. Hypomethylating agents can increase the expression of TEs in cancer cells, inducing ‘viral mimicry’, causing interferon signalling and cancer cell killing. To investigate the role of TEs in the pathogenesis of acute myeloid leukaemia (AML), we studied TE expression in several cell fractions of AML while tracking its development (pre-leukemic haematopoietic stem cells, leukemic stem cells [LSCs], and leukemic blasts). LSCs, which are resistant to chemotherapy and serve as reservoirs for relapse, showed significant suppression of TEs and interferon pathways. Similarly, high-risk cases of myelodysplastic syndrome (MDS) showed far greater suppression of TEs than low-risk cases. We propose TE suppression as a mechanism for immune escape in AML and MDS. Repression of TEs co-occurred with the upregulation of several genes known to modulate TE expression, such as RNA helicases and autophagy genes. Thus, we have identified potential pathways that can be targeted to activate cancer immunogenicity via TEs in AML and MDS.
format	article
author	Anthony R. Colombo Asif Zubair Devi Thiagarajan Sergey Nuzhdin Timothy J. Triche Giridharan Ramsingh
author_facet	Anthony R. Colombo Asif Zubair Devi Thiagarajan Sergey Nuzhdin Timothy J. Triche Giridharan Ramsingh
author_sort	Anthony R. Colombo
title	Suppression of Transposable Elements in Leukemic Stem Cells
title_short	Suppression of Transposable Elements in Leukemic Stem Cells
title_full	Suppression of Transposable Elements in Leukemic Stem Cells
title_fullStr	Suppression of Transposable Elements in Leukemic Stem Cells
title_full_unstemmed	Suppression of Transposable Elements in Leukemic Stem Cells
title_sort	suppression of transposable elements in leukemic stem cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bff7310f125740afb6584afd507b61a5
work_keys_str_mv	AT anthonyrcolombo suppressionoftransposableelementsinleukemicstemcells AT asifzubair suppressionoftransposableelementsinleukemicstemcells AT devithiagarajan suppressionoftransposableelementsinleukemicstemcells AT sergeynuzhdin suppressionoftransposableelementsinleukemicstemcells AT timothyjtriche suppressionoftransposableelementsinleukemicstemcells AT giridharanramsingh suppressionoftransposableelementsinleukemicstemcells
_version_	1718394421476589568

Suppression of Transposable Elements in Leukemic Stem Cells

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