Research Publications

Back

Early lineage priming by trisomy of erg leads to myeloproliferation in a down syndrome model


Ng, AP; Hu, Y; Metcalf, D; Hyland, CD; Ierino, H; Phipson, B; Wu, D; Baldwin, TM; Kauppi, M; Kiu, H; Di Rago, L; Hilton, DJ; Smyth, GK; Alexander, WS
2015-05
PLoS Genet
Journal Article
11
5
e1005211
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.
PLOS
Cancer and Haematology; Bioinformatics; Molecular Medicine
10.1371/journal.pgen.1005211
25973911
Refer to article for additional funding acknowledgements
© 2015 Ng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Download Full Text


Back
Creation Date 2015-05-19 08:21:33 Last Modified 2016-04-20 11:55:37