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- Publisher Website: 10.1182/blood-2010-12-317990
- Scopus: eid_2-s2.0-79959825899
- PMID: 21536859
- WOS: WOS:000292244000016
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Article: ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer
Title | ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer |
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Authors | |
Issue Date | 2011 |
Citation | Blood, 2011, v. 117, n. 26, p. 7079-7089 How to Cite? |
Abstract | The Ets-related gene (ERG) is an Etstranscription factor required for normal blood stem cell development. ERG expression is down-regulated during early Tlymphopoiesis but maintained in T-acute lymphoblastic leukemia (T-ALL), where it is recognized as an independent risk factor for adverse outcome. However, it is unclear whether ERG is directly involved in the pathogenesis of T-ALL and how its expression is regulated. Here we demonstrate that transgenic expression of ERG causes T-ALL in mice and that its knockdown reduces the proliferation of human MOLT4 T-ALL cells. We further demonstrate that ERG expression in primary human T-ALL cells is mediated by the binding of other T-cell oncogenes SCL/TAL1, LMO2, and LYL1 in concert with ERG, FLI1, and GATA3 to the ERG +85 enhancer. This enhancer is not active in normal T cells but in transgenic mice targets expression to fetal liver c-kit + cells, adult bone marrow stem/progenitors and early CD4 - CD8 - doublenegative thymic progenitors. Taken together, these data illustrate that ERG promotes T-ALL and that failure to extinguish activity of stem cell enhancers associated with regulatory transcription factors such as ERG can contribute to the developm ent of leukemia. © 2011 by The American Society of Hematology. |
Persistent Identifier | http://hdl.handle.net/10722/250973 |
ISSN | 2023 Impact Factor: 21.0 2023 SCImago Journal Rankings: 5.272 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Thoms, Julie A.I. | - |
dc.contributor.author | Birger, Yehudit | - |
dc.contributor.author | Foster, Sam | - |
dc.contributor.author | Knezevic, Kathy | - |
dc.contributor.author | Kirschenbaum, Yael | - |
dc.contributor.author | Chandrakanthan, Vashe | - |
dc.contributor.author | Jonquieres, Georg | - |
dc.contributor.author | Spensberger, Dominik | - |
dc.contributor.author | Wong, Jason W. | - |
dc.contributor.author | Oram, S. Helen | - |
dc.contributor.author | Kinston, Sarah J. | - |
dc.contributor.author | Groner, Yoram | - |
dc.contributor.author | Lock, Richard | - |
dc.contributor.author | MacKenzie, Karen L. | - |
dc.contributor.author | Göttgens, Berthold | - |
dc.contributor.author | Izraeli, Shai | - |
dc.contributor.author | Pimanda, John E. | - |
dc.date.accessioned | 2018-02-01T01:54:13Z | - |
dc.date.available | 2018-02-01T01:54:13Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Blood, 2011, v. 117, n. 26, p. 7079-7089 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.uri | http://hdl.handle.net/10722/250973 | - |
dc.description.abstract | The Ets-related gene (ERG) is an Etstranscription factor required for normal blood stem cell development. ERG expression is down-regulated during early Tlymphopoiesis but maintained in T-acute lymphoblastic leukemia (T-ALL), where it is recognized as an independent risk factor for adverse outcome. However, it is unclear whether ERG is directly involved in the pathogenesis of T-ALL and how its expression is regulated. Here we demonstrate that transgenic expression of ERG causes T-ALL in mice and that its knockdown reduces the proliferation of human MOLT4 T-ALL cells. We further demonstrate that ERG expression in primary human T-ALL cells is mediated by the binding of other T-cell oncogenes SCL/TAL1, LMO2, and LYL1 in concert with ERG, FLI1, and GATA3 to the ERG +85 enhancer. This enhancer is not active in normal T cells but in transgenic mice targets expression to fetal liver c-kit + cells, adult bone marrow stem/progenitors and early CD4 - CD8 - doublenegative thymic progenitors. Taken together, these data illustrate that ERG promotes T-ALL and that failure to extinguish activity of stem cell enhancers associated with regulatory transcription factors such as ERG can contribute to the developm ent of leukemia. © 2011 by The American Society of Hematology. | - |
dc.language | eng | - |
dc.relation.ispartof | Blood | - |
dc.title | ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1182/blood-2010-12-317990 | - |
dc.identifier.pmid | 21536859 | - |
dc.identifier.scopus | eid_2-s2.0-79959825899 | - |
dc.identifier.volume | 117 | - |
dc.identifier.issue | 26 | - |
dc.identifier.spage | 7079 | - |
dc.identifier.epage | 7089 | - |
dc.identifier.eissn | 1528-0020 | - |
dc.identifier.isi | WOS:000292244000016 | - |
dc.identifier.issnl | 0006-4971 | - |