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Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()

We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the im...

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Autores principales: Degerman, Sofie, Landfors, Mattias, Siwicki, Jan Konrad, Revie, John, Borssén, Magnus, Evelönn, Emma, Forestier, Erik, Chrzanowska, Krystyna H., Rydén, Patrik, Keith, W. Nicol, Roos, Göran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198827/
https://www.ncbi.nlm.nih.gov/pubmed/25065939
http://dx.doi.org/10.1016/j.neo.2014.07.001
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author Degerman, Sofie
Landfors, Mattias
Siwicki, Jan Konrad
Revie, John
Borssén, Magnus
Evelönn, Emma
Forestier, Erik
Chrzanowska, Krystyna H.
Rydén, Patrik
Keith, W. Nicol
Roos, Göran
author_facet Degerman, Sofie
Landfors, Mattias
Siwicki, Jan Konrad
Revie, John
Borssén, Magnus
Evelönn, Emma
Forestier, Erik
Chrzanowska, Krystyna H.
Rydén, Patrik
Keith, W. Nicol
Roos, Göran
author_sort Degerman, Sofie
collection PubMed
description We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.
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spelling pubmed-41988272014-10-21 Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()() Degerman, Sofie Landfors, Mattias Siwicki, Jan Konrad Revie, John Borssén, Magnus Evelönn, Emma Forestier, Erik Chrzanowska, Krystyna H. Rydén, Patrik Keith, W. Nicol Roos, Göran Neoplasia Article We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis. Neoplasia Press 2014-07-22 /pmc/articles/PMC4198827/ /pubmed/25065939 http://dx.doi.org/10.1016/j.neo.2014.07.001 Text en © 2014 Neoplasia Press, Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Degerman, Sofie
Landfors, Mattias
Siwicki, Jan Konrad
Revie, John
Borssén, Magnus
Evelönn, Emma
Forestier, Erik
Chrzanowska, Krystyna H.
Rydén, Patrik
Keith, W. Nicol
Roos, Göran
Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()
title Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()
title_full Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()
title_fullStr Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()
title_full_unstemmed Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()
title_short Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias()()()
title_sort immortalization of t-cells is accompanied by gradual changes in cpg methylation resulting in a profile resembling a subset of t-cell leukemias()()()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198827/
https://www.ncbi.nlm.nih.gov/pubmed/25065939
http://dx.doi.org/10.1016/j.neo.2014.07.001
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