Journal article
Early Lineage Priming by Trisomy of Erg Leads to Myeloproliferation in a Down Syndrome Model
AP Ng, Y Hu, D Metcalf, CD Hyland, H Ierino, B Phipson, D Wu, TM Baldwin, M Kauppi, H Kiu, L Di Rago, DJ Hilton, GK Smyth, WS Alexander
Plos Genetics | PUBLIC LIBRARY SCIENCE | Published : 2015
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..
View full abstractGrants
Awarded by Australian National Health and Medical Research Council
Funding Acknowledgements
This work was supported by Program and Project Grants (1016647, 1054618), Fellowships (WSA 575501, GKS 1058892), and Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council (https://www.nhmrc.gov.au), the Carden Fellowship (DM) of the Cancer Council, Victoria (http://www.cancervic.org.au), the Cure Cancer Australia (www.cure.org.au/)/Leukaemia Foundation Australia (www.leukaemia.org.au/) Post Doctoral Fellowship and Lions Fellowship, Cancer Council of Victoria (APN), the Australian Cancer Research Fund (http://acrf.com.au) and Victorian State Government Operational Infrastructure Support (www.vic.gov.au). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.