Expression of RUNX1-ETO Rapidly Alters the Chromatin Landscape and Growth of Early Human Myeloid Precursor Cells
Monica Nafria, Peter Keane, Elizabeth S Ng, Edouard G Stanley, Andrew G Elefanty, Constanze Bonifer
Cell Reports | CELL PRESS | Published : 2020
Acute myeloid leukemia (AML) is a hematopoietic malignancy caused by recurrent mutations in genes encoding transcriptional, chromatin, and/or signaling regulators. The t(8;21) translocation generates the aberrant transcription factor RUNX1-ETO (RUNX1-RUNX1T1), which by itself is insufficient to cause disease. t(8;21) AML patients show extensive chromatin reprogramming and have acquired additional mutations. Therefore, the genomic and developmental effects directly and solely attributable to RUNX1-ETO expression are unclear. To address this, we employ a human embryonic stem cell differentiation system capable of forming definitive myeloid progenitor cells to express RUNX1-ETO in an inducible ..View full abstract
Awarded by National Health and Medical Research Council of Australia
This work was funded by a U21 Melbourne studentship and a Wellcome Trust Institutional Strategic Support Fund (ISSF) grant to the University of Birmingham held by M.N., as well as a grant from the Birmingham Cancer Research UK (CRUK) Centre to C.B. We thank the Birmingham Next Generation Sequencing Facility (Genomics Birmingham) for expert service. M.N. was awarded The Henry and Rachael Ackman Travelling Scholarship by the University of Melbourne Faculty of Medicine, Dentistry and Health Sciences. Work in the laboratories of A.G.E. and E. G.S. was funded by the National Health and Medical Research Council of Australia (GNT1068866, GNT1129861, and GNT1138717), the Australian Research Council Special Research Initiative in Stem Cells (Stem Cells Australia), the Children's Cancer Foundation, and the Stafford Fox Medical Research Foundation. E.G. S. (GNT1079004) and A.G.E. (GNT1117596) are research fellows of National Health and Medical Research Council (Australia). Additional infrastructure funding to the Murdoch Children's Research Institute was provided by the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme and the Victorian government's Operational Infrastructure Support Program.