Similar Datasets
Project description:Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signaling genes. It is characterized 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 (GRN), consisting of transcription factors binding to their target genes and imposing a specific gene expression pattern that is required for AML maintenance. In this study, we integrate gene expression, open chromatin and ChIP data with promoter-capture Hi-C data to define a refined core GRN common to all patients with CEBPA-double mutant (CEBPAN/C) AML. These mutations disrupt the structure of a major regulator of myelopoiesis. We identify the binding sites of mutated C/EBPα proteins in primary cells, we show that C/EBPα, AP-1 factors and RUNX1 colocalize and are 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 subtype in human cells.
| S-EPMC9883165 | biostudies-literature
Project description: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.
2022-11-04 | GSE211067 | GEO
Project description: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.
2022-11-04 | GSE211059 | GEO
Project description: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.
2022-11-04 | GSE211094 | GEO
Project description: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.
2022-11-04 | GSE211089 | GEO
Project description: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.
2022-11-04 | GSE211086 | GEO
Project description: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.
2022-11-04 | GSE212104 | GEO
Project description: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.
2022-11-04 | GSE211041 | GEO
Project description: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.
2022-11-04 | GSE211036 | GEO
Project description: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.
2022-11-04 | GSE211028 | GEO