Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 bind...

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Autores principales:	Carolyn Glass, Charles Wuertzer, Xiaohui Cui, Yingtao Bi, Ramana Davuluri, Ying-Yi Xiao, Michael Wilson, Kristina Owens, Yi Zhang, Archibald Perkins
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f6e454064b94a89990b99d6229fd382
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spelling	oai:doaj.org-article:0f6e454064b94a89990b99d6229fd3822021-11-18T07:39:45ZGlobal Identification of EVI1 Target Genes in Acute Myeloid Leukemia.1932-620310.1371/journal.pone.0067134https://doaj.org/article/0f6e454064b94a89990b99d6229fd3822013-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0067134https://doaj.org/toc/1932-6203The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.Carolyn GlassCharles WuertzerXiaohui CuiYingtao BiRamana DavuluriYing-Yi XiaoMichael WilsonKristina OwensYi ZhangArchibald PerkinsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e67134 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carolyn Glass Charles Wuertzer Xiaohui Cui Yingtao Bi Ramana Davuluri Ying-Yi Xiao Michael Wilson Kristina Owens Yi Zhang Archibald Perkins Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
description	The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.
format	article
author	Carolyn Glass Charles Wuertzer Xiaohui Cui Yingtao Bi Ramana Davuluri Ying-Yi Xiao Michael Wilson Kristina Owens Yi Zhang Archibald Perkins
author_facet	Carolyn Glass Charles Wuertzer Xiaohui Cui Yingtao Bi Ramana Davuluri Ying-Yi Xiao Michael Wilson Kristina Owens Yi Zhang Archibald Perkins
author_sort	Carolyn Glass
title	Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
title_short	Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
title_full	Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
title_fullStr	Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
title_full_unstemmed	Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
title_sort	global identification of evi1 target genes in acute myeloid leukemia.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0f6e454064b94a89990b99d6229fd382
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Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

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