ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.

High expression of the E26 transforming sequence related gene (ERG) is associated with poor prognosis in a subgroup of leukemia patients with acute myeloid (AML) and acute T-lymphoblastic leukemia (T-ALL). In a previous study we proposed that ERG overexpression may deregulate several signaling casca...

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Autores principales:	Juliane Bock, Liliana H Mochmann, Cornelia Schlee, Nasrin Farhadi-Sartangi, Stefanie Göllner, Carsten Müller-Tidow, Claudia D Baldus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b25b4eced5084ebe887e88f653624dea
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spelling	oai:doaj.org-article:b25b4eced5084ebe887e88f653624dea2021-11-18T08:02:48ZERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.1932-620310.1371/journal.pone.0052872https://doaj.org/article/b25b4eced5084ebe887e88f653624dea2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300998/?tool=EBIhttps://doaj.org/toc/1932-6203High expression of the E26 transforming sequence related gene (ERG) is associated with poor prognosis in a subgroup of leukemia patients with acute myeloid (AML) and acute T-lymphoblastic leukemia (T-ALL). In a previous study we proposed that ERG overexpression may deregulate several signaling cascades in acute leukemia. Herein, we further expand those studies by identifying a consensus of biological targets in primary blasts of newly diagnosed acute leukemia patients. Our findings of chromatin immunoprecipitation-on-chip of primary samples revealed 48 significantly enriched single genes including DAAM1 and NUMB. Significantly enriched signaling pathways included WNT/β-catenin, p53, and PI3K/AKT with ERG overexpression inducing dephosphorylation of AKT(Ser473) relative to non ERG expressing K562 cells. Cell based ERG overexpression studies also revealed drug resistance to multi-kinase inhibitor, BAY 43-9006 (Sorafenib) and to the tyrosine kinase inhibitor TKI258. Thus in primary leukemic cells, ERG may contribute to the dysregulation of kinase signaling, which results in resistance to kinase inhibitors.Juliane BockLiliana H MochmannCornelia SchleeNasrin Farhadi-SartangiStefanie GöllnerCarsten Müller-TidowClaudia D BaldusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e52872 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Juliane Bock Liliana H Mochmann Cornelia Schlee Nasrin Farhadi-Sartangi Stefanie Göllner Carsten Müller-Tidow Claudia D Baldus ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.
description	High expression of the E26 transforming sequence related gene (ERG) is associated with poor prognosis in a subgroup of leukemia patients with acute myeloid (AML) and acute T-lymphoblastic leukemia (T-ALL). In a previous study we proposed that ERG overexpression may deregulate several signaling cascades in acute leukemia. Herein, we further expand those studies by identifying a consensus of biological targets in primary blasts of newly diagnosed acute leukemia patients. Our findings of chromatin immunoprecipitation-on-chip of primary samples revealed 48 significantly enriched single genes including DAAM1 and NUMB. Significantly enriched signaling pathways included WNT/β-catenin, p53, and PI3K/AKT with ERG overexpression inducing dephosphorylation of AKT(Ser473) relative to non ERG expressing K562 cells. Cell based ERG overexpression studies also revealed drug resistance to multi-kinase inhibitor, BAY 43-9006 (Sorafenib) and to the tyrosine kinase inhibitor TKI258. Thus in primary leukemic cells, ERG may contribute to the dysregulation of kinase signaling, which results in resistance to kinase inhibitors.
format	article
author	Juliane Bock Liliana H Mochmann Cornelia Schlee Nasrin Farhadi-Sartangi Stefanie Göllner Carsten Müller-Tidow Claudia D Baldus
author_facet	Juliane Bock Liliana H Mochmann Cornelia Schlee Nasrin Farhadi-Sartangi Stefanie Göllner Carsten Müller-Tidow Claudia D Baldus
author_sort	Juliane Bock
title	ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.
title_short	ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.
title_full	ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.
title_fullStr	ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.
title_full_unstemmed	ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.
title_sort	erg transcriptional networks in primary acute leukemia cells implicate a role for erg in deregulated kinase signaling.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b25b4eced5084ebe887e88f653624dea
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ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling.

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