Early lineage priming by trisomy of Erg leads to myeloproliferation in a Down syndrome model.
PLoS Genet
; 11(5): e1005211, 2015 May.
Article
en 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Madre
/
Factores de Transcripción
/
Trisomía
/
Cromosomas Humanos Par 21
/
Transactivadores
/
Proteínas Oncogénicas
/
Síndrome de Down
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Australia