Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias

Tursky, ML; Beck, D; Thoms, JAI; Huang, Y; Kumari, A; Unnikrishnan, A; Knezevic, K; Evans, K; Richards, LA; Lee, E; Morris, J; Goldberg, L; Izraeli, S; Wong, JWH; Olivier, J; Lock, RB; MacKenzie, KL; Pimanda, JE

Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias

Tursky, ML Beck, D Thoms, JAI Huang, Y

Kumari, A Unnikrishnan, A Knezevic, K Evans, K Richards, LA Lee, E Morris, J Goldberg, L Izraeli, S Wong, JWH Olivier, J Lock, RB MacKenzie, KL Pimanda, JE

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Publication Type:: Journal Article
Citation:: Leukemia, 2015, 29 (4), pp. 819 - 827
Issue Date:: 2015-04-15

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Field	Value	Language
dc.contributor.author	Tursky, ML	en_US
dc.contributor.author	Beck, D	en_US
dc.contributor.author	Thoms, JAI	en_US
dc.contributor.author	Huang, Y https://orcid.org/0000-0002-7003-3110	en_US
dc.contributor.author	Kumari, A	en_US
dc.contributor.author	Unnikrishnan, A	en_US
dc.contributor.author	Knezevic, K	en_US
dc.contributor.author	Evans, K	en_US
dc.contributor.author	Richards, LA	en_US
dc.contributor.author	Lee, E	en_US
dc.contributor.author	Morris, J	en_US
dc.contributor.author	Goldberg, L	en_US
dc.contributor.author	Izraeli, S	en_US
dc.contributor.author	Wong, JWH	en_US
dc.contributor.author	Olivier, J	en_US
dc.contributor.author	Lock, RB	en_US
dc.contributor.author	MacKenzie, KL	en_US
dc.contributor.author	Pimanda, JE	en_US
dc.date.available	2014-10-03	en_US
dc.date.issued	2015-04-15	en_US
dc.identifier.citation	Leukemia, 2015, 29 (4), pp. 819 - 827	en_US
dc.identifier.issn	0887-6924	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132444
dc.description.abstract	© 2015 Macmillan Publishers Limited. High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia.	en_US
dc.relation.ispartof	Leukemia	en_US
dc.relation.isbasedon	10.1038/leu.2014.299	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Stem Cells	en_US
dc.subject.mesh	Fetal Blood	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Retroviridae	en_US
dc.subject.mesh	Cell Transformation, Neoplastic	en_US
dc.subject.mesh	Trans-Activators	en_US
dc.subject.mesh	Antigens, CD34	en_US
dc.subject.mesh	Transduction, Genetic	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Mutation	en_US
dc.subject.mesh	Genetic Vectors	en_US
dc.subject.mesh	Leukemia, Myeloid, Acute	en_US
dc.subject.mesh	High-Throughput Nucleotide Sequencing	en_US
dc.subject.mesh	Transcriptome	en_US
dc.subject.mesh	Transcriptional Regulator ERG	en_US
dc.title	Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	29	en_US
utslib.for	1112 Oncology and Carcinogenesis	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	0903 Biomedical Engineering	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Software
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	29	en_US

Abstract:

© 2015 Macmillan Publishers Limited. High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/132444