Gfi1 as a new predictive and therapeutical target of MDS/AML
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE72671 |
| Title | Gfi1 as a new predictive and therapeutical target of MDS/AML |
| Description | MDS is characterized by a disturbed function of the myeloid lineage of the hematopoietic system that may transform to AML, a malignant disease of the myeloid compartment. Epigenetic and genetic aberrations contribute to the initiation and progression of MDS/AML. GFI1 is a transcriptional repressor, which regulates expression of its target genes by, among other approaches, recruiting HDACs to its target genes to remove histone 3 lysine 9 (H3K9) acetylation, a marker for active gene expression. Low levels of GFI1 expression and deletion of one GFI1 allele contribute to MDS/AML development in human patients and are associated with a specific gene expression signature and inferior prognosis. To explore the mechanism behind this, we used a mouse strain, which expresses GFI1 only at 5-10%% of the normal level (GFI1-Knock-down (KD)). Knock-down of GFI1 or loss of one murine Gfi1 allele reduced latency and increased incidence of AML in different murine models of human MDS/AML development. On the epigenetic level, KD of Gfi1 lead to increased amount of H3K9 acetylation, resulting in increased expression of genes involved in AML development. On a translational level both murine as well as human AML cells with low expression of GFI1 are resistant to standard epigenetic therapy. We show that treatment with histone acetyltransferase inhibitors might be a novel treatment approach for low Gfi1-expressing blast cells. GFI1 has a dose dependent role in myeloid malignancies and is a biomarker for therapeutic intervention. We carried out ChIP-Seq Analysis of H3K9Ac and RNA-Seq in leukemic cells from mice expressing reduced levels of Gfi1 compared to controls expressing normal levels of the factor. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72671 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE48048
Gene expression profiling normal murine myeloid cells and myeloid leukemia cells induced by CNTRL-FGFR1
1
GSE70239
Using single-cell RNA-Seq for unbiased analysis of developmental hierarchies (single cell RNA Seq of Gfi1-/- GMP)
1
GSE78907
Using single-cell RNA-Seq for unbiased analysis of developmental hierarchies (single cell RNA Seq of Gfi1-/- Irf8-/- GMP)
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
