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| Status |
Public on Mar 31, 2018 |
| Title |
Gfi1b - A key player in genesis and maintenance of AML and MDS [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Differentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
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| Overall design |
one sample per genotype has been sequenced
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| Contributor(s) |
Thivakaran A, Botezatu L, Hönes J, Schütte J, Vassen L, Olberding N, Al-Matary YS, Köster R, Lennartz K, Görgens A, Giebel B, Opalka B, Dührsen U, Khandanpour C |
| Citation(s) |
29326122 |
| Submission date |
Oct 19, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Cyrus Khandanpour |
| E-mail(s) |
cyrus.khandanpour@uk-essen.de
|
| Organization name |
University Hospital Of Essen
|
| Department |
Department of Hematology
|
| Lab |
WTZ-Forschungsgebäude 2.OG
|
| Street address |
Hufelandstr. 55
|
| City |
Essen |
| State/province |
NRW |
| ZIP/Postal code |
45147 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE88935 |
Gfi1b - A key player in genesis and maintenance of AML and MDS |
|
| Relations |
| BioProject |
PRJNA349148 |
| SRA |
SRP091765 |
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