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Early Lineage Priming by Trisomy of Erg Leads to Myeloproliferation in a Down Syndrome Model
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نویسنده
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ng a.p. ,hu y. ,metcalf d. ,hyland c.d. ,ierino h. ,phipson b. ,wu d. ,baldwin t.m. ,kauppi m. ,kiu h. ,di rago l. ,hilton d.j. ,smyth g.k. ,alexander w.s.
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منبع
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plos genetics - 2015 - دوره : 11 - شماره : 5
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چکیده
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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. © 2015 ng et al.
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آدرس
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the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,the university of melbourne,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,the university of melbourne,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of mathematics and statistics,the university of melbourne,parkville,vic, Australia, centre for cancer research,monash institute of medical research,monash university,clayton,vic,australia,department of statistics,harvard university,cambridge,ma, United States, the walter and eliza hall institute of medical research,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,the university of melbourne,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,the university of melbourne,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,the university of melbourne,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of mathematics and statistics,the university of melbourne,parkville,vic, Australia, the walter and eliza hall institute of medical research,parkville,vic,australia,department of medical biology,the university of melbourne,parkville,vic, Australia
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Authors
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