Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia

Abstract T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mu...

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Autores principales:	Shulan Tian, Henan Zhang, Pan Zhang, Michael Kalmbach, Jeong-Heon Lee, Tamas Ordog, Paul J. Hampel, Timothy G. Call, Thomas E. Witzig, Neil E. Kay, Eric W. Klee, Susan L. Slager, Huihuang Yan, Wei Ding
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43304e766b734189afed60f90539ff6d
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spelling	oai:doaj.org-article:43304e766b734189afed60f90539ff6d2021-12-02T14:27:45ZEpigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia10.1038/s41598-021-87890-92045-2322https://doaj.org/article/43304e766b734189afed60f90539ff6d2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87890-9https://doaj.org/toc/2045-2322Abstract T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mutations were also identified in genes encoding chromatin regulators and those in the JAK-STAT signaling pathway. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL, limiting the mechanistic study of its carcinogenesis. We hypothesize epigenetic mechanisms also play a key role in T-PLL pathogenesis. To systematically test this hypothesis, we generated genome-wide maps of regulatory regions using H3K4me3 and H3K27ac ChIP-seq, as well as RNA-seq data in both T-PLL patients and healthy individuals. We found that genes down-regulated in T-PLL are mainly associated with defense response, immune system or adaptive immune response, while up-regulated genes are enriched in developmental process, as well as WNT signaling pathway with crucial roles in cell fate decision. In particular, our analysis revealed a global alteration of regulatory landscape in T-PLL, with differential peaks highly enriched for binding motifs of immune related transcription factors, supporting the epigenetic regulation of oncogenes and genes involved in DNA damage response and T-cell activation. Together, our work reveals a causal role of epigenetic dysregulation in T-PLL.Shulan TianHenan ZhangPan ZhangMichael KalmbachJeong-Heon LeeTamas OrdogPaul J. HampelTimothy G. CallThomas E. WitzigNeil E. KayEric W. KleeSusan L. SlagerHuihuang YanWei DingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shulan Tian Henan Zhang Pan Zhang Michael Kalmbach Jeong-Heon Lee Tamas Ordog Paul J. Hampel Timothy G. Call Thomas E. Witzig Neil E. Kay Eric W. Klee Susan L. Slager Huihuang Yan Wei Ding Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
description	Abstract T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mutations were also identified in genes encoding chromatin regulators and those in the JAK-STAT signaling pathway. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL, limiting the mechanistic study of its carcinogenesis. We hypothesize epigenetic mechanisms also play a key role in T-PLL pathogenesis. To systematically test this hypothesis, we generated genome-wide maps of regulatory regions using H3K4me3 and H3K27ac ChIP-seq, as well as RNA-seq data in both T-PLL patients and healthy individuals. We found that genes down-regulated in T-PLL are mainly associated with defense response, immune system or adaptive immune response, while up-regulated genes are enriched in developmental process, as well as WNT signaling pathway with crucial roles in cell fate decision. In particular, our analysis revealed a global alteration of regulatory landscape in T-PLL, with differential peaks highly enriched for binding motifs of immune related transcription factors, supporting the epigenetic regulation of oncogenes and genes involved in DNA damage response and T-cell activation. Together, our work reveals a causal role of epigenetic dysregulation in T-PLL.
format	article
author	Shulan Tian Henan Zhang Pan Zhang Michael Kalmbach Jeong-Heon Lee Tamas Ordog Paul J. Hampel Timothy G. Call Thomas E. Witzig Neil E. Kay Eric W. Klee Susan L. Slager Huihuang Yan Wei Ding
author_facet	Shulan Tian Henan Zhang Pan Zhang Michael Kalmbach Jeong-Heon Lee Tamas Ordog Paul J. Hampel Timothy G. Call Thomas E. Witzig Neil E. Kay Eric W. Klee Susan L. Slager Huihuang Yan Wei Ding
author_sort	Shulan Tian
title	Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
title_short	Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
title_full	Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
title_fullStr	Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
title_full_unstemmed	Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia
title_sort	epigenetic alteration contributes to the transcriptional reprogramming in t-cell prolymphocytic leukemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/43304e766b734189afed60f90539ff6d
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Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia

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