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Series GSE47003 Query DataSets for GSE47003
Status Public on Dec 10, 2013
Title Initiation of MLL-rearranged AML is orchestrated by C/EBPa
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Acute Myeloid Leukemia (AML) is associated with a number of genetic and epigenetic events that result in malignant transformation of hematopoietic cells. In particular, transcription factors essential for normal hematopoiesis and stem cell function are often found mutated leading to the formation of leukemic stem cells and the accumulation of immature blasts. Among them, translocations involving the mixed lineage leukemia (MLL) gene at chromosome band 11q23 are one of the most commonly events (~10 %) and is associated with poor prognosis in human leukemias. Whereas the downstream effects of MLL-fusion proteins are well established, the modes on which these effects are mediated are still unclear and whether MLL-fusion proteins are dependent on other transcriptional regulators or act alone remains elusive. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBPα to be up-regulated in the AML samples, suggesting that C/EBPα might collaborate with MLL-fusion proteins in the initial transformation process. We could show that transformation by MLL-fusion proteins is dependent on C/EBPα activity both in early progenitors as well as in GMPs. In contrast, C/EBPα was found to be indispensable in an already established leukemia. These finding led us to study the early transcriptional changes induced by MLL-ENL expression and we identified a combined C/EBPα / MLL-ENL transcriptional signature. Collectivly, our data shows that C/EBPα configure a proper chromatin state required for MLL-fusions to induce malignant transformation.
Overall design Histone modification profiles (H3K4me3 and H3K27me3) in haematopoietic progenitor cells (preGM, wild type and Cebpa knock out), and C/EBPα binding in GMP cells
Contributor(s) Ohlsson E, Porse BT
Citation(s) 24367003
Submission date May 16, 2013
Last update date May 15, 2019
Contact name Bo Torben Porse
Phone +45 3545 6023
Organization name University of Copenhagen/Rigshospitalet
Department BRIC/Finsen Laboratory
Lab Porse group
Street address Ole Maaloes vej 5
City Copenhagen
ZIP/Postal code 2200
Country Denmark
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (11)
GSM1142801 ChIP-seq_K4me3_preGM_CebpaWT
GSM1142802 ChIP-seq_K4me3_preGM_CebpaWT_replicate
GSM1142803 ChIP-seq_K4me3_preGM_CebpaKO
BioProject PRJNA203263
SRA SRP022847

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE47003_GMP_merged_peaks.txt.gz 376.6 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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