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Series GSE80773 Query DataSets for GSE80773
Status Public on Oct 30, 2017
Title AML1-ETO-induced FOXO1 activates a self-renewal program in pre-leukemia stem cells
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Blocking the self-renewal of pre-leukemia stem cells could prevent AML relapse. In this study we show that FOXO1 is an essential self-renewal factor in leukemic and pre-leukemic cells expressing the t(8;21)-associated oncogene AML1-ETO (AE). FOXO1 is consistently upregulated in t(8;21) AML and functions as a critical oncogenic mediator rather than a tumor suppressor. Expression of FOXO1 in human CD34+ cells promotes a pre-leukemic state, partially phenocopying the cellular and transcriptional effects of AE expression. The DNA binding ability of FOXO1 is essential for these features. AE and FOXO1 co-occupy the majority of their binding sites, whereby FOXO1 binds to multiple crucial self-renewal genes and is required for their activation. In concordance with this observation, loss of FOXO1 inhibits the long-term proliferation and clonogenicity of AE cells. Thus, increased FOXO1 represents a new mechanism for acquiring aberrant self-renewal by pre-leukemia stem cells and provides a novel target for therapeutic intervention.
Overall design AE and FOXO1 ChIP-seq expreiment have been used to study their activates in pre-leukemia stem cells
Contributor(s) Lin S, Ptasinska A, Chen X, Shretha M, Assi SA, Chin PS, Imperato MR, Aronow B, Zhang J, Weirauch MT, Bonifer C, Mulloy JC
Citation(s) 28710059
Submission date Apr 28, 2016
Last update date May 15, 2019
Contact name Salam Adli Assi
Organization name University of Birmingham
Department Institute for Cancer and Genomic Sciences
Street address IBR
City Birmingham
ZIP/Postal code B15 2TT
Country United Kingdom
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (2)
GSM2136845 AE_ChIPSeq
GSM2136846 FOXO1_ChIPSeq
BioProject PRJNA319962
SRA SRP074132

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Supplementary file Size Download File type/resource
GSE80773_RAW.tar 680.2 Mb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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