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| 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
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| 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.
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| Overall design |
AE and FOXO1 ChIP-seq expreiment have been used to study their activates in pre-leukemia stem cells
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| 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 |
| E-mail(s) |
s.a.assi@bham.ac.uk
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| Organization name |
University of Birmingham
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| Department |
Institute for Cancer and Genomic Sciences
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| Street address |
IBR
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| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA319962 |
| SRA |
SRP074132 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80773_RAW.tar |
680.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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