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| Status |
Public on Nov 04, 2022 |
| Title |
Identification and interrogation of the gene regulatory network of CEBPA double mutant Acute Myeloid Leukaemia [Patient RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Acute myeloid leukaemia (AML) is a heterogeneous haematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signalling genes. It is characterised by a disturbance of differentiation and abnormal proliferation of hematopoietic progenitors. We have previously shown that each AML subtype establishes its own core gene regulatory network, consisting of transcription factors binding to their target genes and imposing a specific gene expression pattern that is required for AML maintenance. In the study presented here, we integrate gene expression, open chromatin and ChIP data, with promoter-capture HiC data to define a refined core gene regulatory network common to all patients with one CEBPA N-terminal mutation plus one C- terminal mutation that each disrupt the structure of a major regulator of myelopoiesis (CEBPAN/C AML). We identify the binding sites of mutated C/EBPα proteins in primary cells, we show that the C/EBP family, AP-1 factors and RUNX1 colocalise and are all required for AML maintenance, and we employ single cell experiments to link important network nodes to the specific differentiation trajectory from leukemic stem to blast cells. Taken together, our study provides an important resource which predicts the specific therapeutic vulnerabilities of this AML sub-type in human cells.
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| Overall design |
Gene expression profiling (RNA-Seq) of sorted CD34+ CEBPA double-mutant primary cells
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| Contributor(s) |
Adamo A, Chin P, Keane P, Assi S, Potluri S, Kellaway SG, Coleman D, Ptasinska A, Delwel HR, Cockerill PN, Bonifer C |
| Citation(s) |
36333583 |
| |
| Submission date |
Aug 11, 2022 |
| Last update date |
Feb 03, 2023 |
| Contact name |
Peter Keane |
| E-mail(s) |
p.keane@bham.ac.uk
|
| Organization name |
University of Birmingham
|
| Department |
Institute for Cancer and Genomic Sciences
|
| Street address |
Vincent Drive
|
| City |
Birmingham |
| ZIP/Postal code |
B15 2TT |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE211095 |
Identification and interrogation of the gene regulatory network of CEBPA double mutant Acute Myeloid Leukaemia |
|
| Relations |
| BioProject |
PRJNA868802 |
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