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Early lineage priming by trisomy of Erg leads to myeloproliferation in a Down syndrome model.
Ng, Ashley P; Hu, Yifang; Metcalf, Donald; Hyland, Craig D; Ierino, Helen; Phipson, Belinda; Wu, Di; Baldwin, Tracey M; Kauppi, Maria; Kiu, Hiu; Di Rago, Ladina; Hilton, Douglas J; Smyth, Gordon K; Alexander, Warren S.
Afiliação
  • Ng AP; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Hu Y; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Metcalf D; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Hyland CD; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Ierino H; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Phipson B; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia.
  • Wu D; Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; Department of Statistics, Harvard University, Cambridge, Massachusetts, United States of America.
  • Baldwin TM; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Kauppi M; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Kiu H; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Di Rago L; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
  • Hilton DJ; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Smyth GK; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia.
  • Alexander WS; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
PLoS Genet ; 11(5): e1005211, 2015 May.
Article em En | MEDLINE | ID: mdl-25973911
ABSTRACT
Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS foetal livers precede the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We demonstrate here that genetic changes specifically attributable to trisomy of Erg lead to lineage priming of primitive and early multipotential progenitor cells in Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant myeloproliferation. Gene expression changes dependent on trisomy of Erg in Ts(1716)65Dn multilineage progenitor cells were correlated with those associated with trisomy of HSA21 in human DS hematopoietic stem and primitive progenitor cells. These data suggest a role for ERG as a regulator of hematopoietic lineage potential, and that trisomy of ERG in the context of DS foetal liver hemopoiesis drives the pre-leukemic changes that predispose to subsequent DS-TMD and DS-AMKL.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Fatores de Transcrição / Trissomia / Cromossomos Humanos Par 21 / Transativadores / Proteínas Oncogênicas / Síndrome de Down Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Fatores de Transcrição / Trissomia / Cromossomos Humanos Par 21 / Transativadores / Proteínas Oncogênicas / Síndrome de Down Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article