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Article: Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia

TitleActivity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia
Authors
Issue Date2013
Citation
Blood, 2013, v. 121, n. 12, p. 2289-2300 How to Cite?
Abstract© 2013 by The American Society of Hematology. Aberrant transcriptional programs in combination with abnormal proliferative signaling drive leukemic transformation. These programs operate in normal hematopoiesis where they are involved in hematopoietic stem cell (HSC) proliferation and maintenance. Ets Related Gene (ERG) is a component of normal and leukemic stem cell signatures and high ERG expression is a risk factor for poor prognosis in acute (AML). However, mechanisms that underlie ERG expression in AML and how its expression relates to leukemic stemness are unknown. We report that ERG expression in AML is associated with activity of the ERG promoters and +85 stem cell enhancer and a heptad of transcription factors that combinatorially regulate genes in HSCs. Gene expression signatures derived from ERG promoterâ stem cell enhancer and heptad activity are associated with clinical outcome when ERG expression alone fails. We also show that the heptad signature is associated with AMLs that lack somatic mutations in NPM1 and confers an adverse prognosis when associated with FLT3 mutations. Taken together, these results suggest that transcriptional regulators cooperate to establish or maintain primitive stem cellâ like signatures in leukemic cells and that the underlying pattern of somatic mutations contributes to the development of these signatures and modulate their influence on clinical outcome.
Persistent Identifierhttp://hdl.handle.net/10722/251037
ISSN
2023 Impact Factor: 21.0
2023 SCImago Journal Rankings: 5.272
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDiffner, Eva-
dc.contributor.authorBeck, Dominik-
dc.contributor.authorGudgin, Emma-
dc.contributor.authorThoms, Julie A.I.-
dc.contributor.authorKnezevic, Kathy-
dc.contributor.authorPridans, Clare-
dc.contributor.authorFoster, Sam-
dc.contributor.authorGoode, Debbie-
dc.contributor.authorLim, Weng Khong-
dc.contributor.authorBoelen, Lies-
dc.contributor.authorMetzeler, Klaus H.-
dc.contributor.authorMicklem, Gos-
dc.contributor.authorBohlander, Stefan K.-
dc.contributor.authorBuske, Christian-
dc.contributor.authorBurnett, Alan-
dc.contributor.authorOttersbach, Katrin-
dc.contributor.authorVassiliou, George S.-
dc.contributor.authorOlivier, Jake-
dc.contributor.authorWong, Jason W.H.-
dc.contributor.authorGöttgens, Berthold-
dc.contributor.authorHuntly, Brian J.-
dc.contributor.authorPimanda, John E.-
dc.date.accessioned2018-02-01T01:54:24Z-
dc.date.available2018-02-01T01:54:24Z-
dc.date.issued2013-
dc.identifier.citationBlood, 2013, v. 121, n. 12, p. 2289-2300-
dc.identifier.issn0006-4971-
dc.identifier.urihttp://hdl.handle.net/10722/251037-
dc.description.abstract© 2013 by The American Society of Hematology. Aberrant transcriptional programs in combination with abnormal proliferative signaling drive leukemic transformation. These programs operate in normal hematopoiesis where they are involved in hematopoietic stem cell (HSC) proliferation and maintenance. Ets Related Gene (ERG) is a component of normal and leukemic stem cell signatures and high ERG expression is a risk factor for poor prognosis in acute (AML). However, mechanisms that underlie ERG expression in AML and how its expression relates to leukemic stemness are unknown. We report that ERG expression in AML is associated with activity of the ERG promoters and +85 stem cell enhancer and a heptad of transcription factors that combinatorially regulate genes in HSCs. Gene expression signatures derived from ERG promoterâ stem cell enhancer and heptad activity are associated with clinical outcome when ERG expression alone fails. We also show that the heptad signature is associated with AMLs that lack somatic mutations in NPM1 and confers an adverse prognosis when associated with FLT3 mutations. Taken together, these results suggest that transcriptional regulators cooperate to establish or maintain primitive stem cellâ like signatures in leukemic cells and that the underlying pattern of somatic mutations contributes to the development of these signatures and modulate their influence on clinical outcome.-
dc.languageeng-
dc.relation.ispartofBlood-
dc.titleActivity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1182/blood-2012-07-446120-
dc.identifier.pmid23327922-
dc.identifier.scopuseid_2-s2.0-84877930760-
dc.identifier.volume121-
dc.identifier.issue12-
dc.identifier.spage2289-
dc.identifier.epage2300-
dc.identifier.eissn1528-0020-
dc.identifier.isiWOS:000321761100019-
dc.identifier.issnl0006-4971-

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