GEO DataSets

(Submitter supplied) The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPADM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPANT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. CEBPADM AML features recurrent co-occurring mutations including GATA2 lesions, however insights into mechanisms governing this co-mutational spectrum are incomplete. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

6 Samples

Download data: TSV

(Submitter supplied) The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPADM) in acute myeloid leukemia (AML); with a combination of hypermorphic N-terminal mutations (CEBPANT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. CEBPADM AML features recurrent co‑occurring mutations; however, insight into the underlying mechanisms for the co-mutational spectra is incomplete. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL21103 GPL30172

24 Samples

Download data: BED, BW, TXT, XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platform:

GPL19057

11 Samples

Download data: TSV, TXT

(Submitter supplied) The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPADM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPANT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. CEBPADM AML features recurrent co-occurring mutations including GATA2 lesions, however insights into mechanisms governing this co-mutational spectrum are incomplete. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL19057

5 Samples

Download data: TXT

(Submitter supplied) We mapped p30-associated regulatory elements by ATAC-seq and ChIP-seq in a myeloid progenitor cell model for p30-driven AML that enables inducible RNAi-mediated knockdown of p30. Concomitant p30-dependent changes in gene expression were measured by RNA-seq. Integrative analysis identified 117 p30-dependent regulatory elements associated with 33 strongly down-regulated genes upon p30-knockdown.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL21493 GPL17021

23 Samples

Download data: BW, TXT

(Submitter supplied) Epigenetic regulators are frequently mutated in acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers impacting on AML biology will not only improve our basic understanding of AML but may also uncover novel options for therapeutic intervention. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

16 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

39 Samples

Download data: BEDGRAPH, BW

(Submitter supplied) Epigenetic regulators are frequently mutated in acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers impacting on AML biology will not only improve our basic understanding of AML but may also uncover novel options for therapeutic intervention. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

10 Samples

Download data: BEDGRAPH

(Submitter supplied) Epigenetic regulators are frequently mutated in hematological malignancies including acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors, and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers affecting AML biology will not only improve our basic understanding of AML, but can also uncover novel options for therapeutic intervention. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

13 Samples

Download data: BW

(Submitter supplied) CEBPA is a key hematopoietic transcription factor (TF), found mutated in 5-14% of all acute myeloid leukemia (AML) cases, but the direct molecular ramifications of this driver mutation remains elusive. To investigate CEBPA-mutant AML, we compared patient aberrant genetic programs with changes in a precise mouse model (Lp30) expressing only the cancer-prevalent truncated CEBPA, p30, and identified a stringent cross-species AML program. more...

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL19057 GPL11154 GPL13112

35 Samples

Download data: BW, XLSX

(Submitter supplied) Acute myeloid leukemia (AML) with CEBPA mutations is determined as provisional entity in the current WHO. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon dm cases were shown to be associated with longer overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

38 Samples

Download data: CEL

(Submitter supplied) The gene encoding the transcription factor C/EBPα is mutated in 10-15% of all patients with de novo acute myeloid leukemia (AML). N-terminal CEBPA mutations cause selective ablation of full-length C/EBPα without affecting the expression of a shorter oncogenic isoform, termed p30. The mechanistic basis of p30-induced leukemogenesis is not well understood. Here, we show that the SET/MLL histone methyltransferase complex represents a critical actionable vulnerability in CEBPA-mutated AML. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL17021 GPL21103

20 Samples

Download data: BW, TXT

(Submitter supplied) The clinical impact of aberrant CEBPA promoter methylation (PM) in AML is controversial discussed. The aim of this study was to clarify the significance of aberrant CEBPA PM with regard to clinical features in a cohort of 572 de novo AML with wildtype CEBPA and normal karyotype. The distal promoter was methylated in 54/572 cases (9.41%) whereas proximal PM was never detected. Methylation of the core promoter was detected in only 8 of 326 cases (2.45%) and thus seems to be a rare event in AML. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

37 Samples

Download data: CEL

(Submitter supplied) Disruption of epigenetic regulation is a hallmark of Acute Myeloid Leukemia (AML), but therapeutic interventions are difficult by the interplay of epigenetic mechanisms controlling genomic elements. We hypothesized that concurrent targeting of aberrant promoter and enhancer epigenetic silencing improves efficacy against AML. To test this, we developed an ex vivo culturing system and treated 52 patient-derived AML with low-dose 5-Azacytidine and specific LSD1 inhibitors. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platform:

GPL16791

28 Samples

Download data: TXT

(Submitter supplied) Chromosomal aberrations in acute myeloid leukemia (AML), such as inv(3) and t(3;3), lead to deregulation of the EVI1 oncogene by the GATA2 distal hematopoietic enhancer (G2DHE). In this project, we aimed to study the transcription factor complexes involved in the regulation of the G2DHE sequence. We have identified PARPi as a member of the G2DHE complex. Here, we used RNA-Seq to analyze transcriptomic changes after PARP inhibition with olaparib and talazoparib and to compare those to EVI1 knockdown.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

16 Samples

Download data: TSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Other; Expression profiling by high throughput sequencing

Platforms:

GPL20301 GPL11154

21 Samples

Download data: BW, TSV

(Submitter supplied) Chromosomal aberrations in acute myeloid leukemia (AML), such as inv(3) and t(3;3), lead to deregulation of the EVI1 oncogene by the GATA2 distal hematopoietic enhancer (G2DHE). In this project, we aimed to study the transcription factor complexes involved in the regulation of the G2DHE sequence. We identified PARP1 as an interactor of G2DHE-associated transcription factors. In this dataset, we studied the interaction of genomic loci between the EVI1 promoter and G2DHE by 4C-Seq in the 3q-rearranged AML cell line MUTZ-3 treated with the PARP1 inhibitors olaparib, talazoparib or the DMSO vehicle control for 24 h.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL11154

3 Samples

Download data: BW

(Submitter supplied) Chromosomal aberrations in acute myeloid leukemia (AML), such as inv(3) and t(3;3), lead to deregulation of the EVI1 oncogene by the GATA2 distal hematopoietic enhancer (G2DHE). In this project, we aimed to study the transcription factor complexes involved in the regulation of the G2DHE sequence. In silico and in vitro analyses revealed that binding sites for CEBPA are critical for G2DHE function. Here, we used ChIP-Seq to show association of the CEBPA transcription factor with the G2DHE sequence in the 3q-rearranged cell line MOLM-1

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

2 Samples

Download data: BW

(Submitter supplied) The study was a comparison of gene expression using RNA-seq. We analyzed the stem and progenitor cells from WT and Vav-cre+ Tet2fl/fl Flt3-ITD (T2F3) mice. We isolated stem cells LSK (lin- sca+ kit+) and granulocyte-macrophage progenitors GMP (lin- sca- kit+ fcgr+ cd34+) cells from bone marrow. Comparisons were made across genotypes WT vs. T2F3 and cell types LSK vs. GMP.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18635

12 Samples

Download data: TXT

(Submitter supplied) Studies of AML patient samples have shown that specific combinations of AML disease alleles confer an adverse outcome, however, in vivo models do not exist for the majority of common, poor-prognosis genotypes. Here we show that TET2/FLT3 mutations can cooperate to induce AML in vivo using a genetically engineered mouse model, and that this model has a defined stem-cell population with a characteristic transcriptional and epigenetic profile. more...

Organism:

Mus musculus; Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platforms:

GPL13112 GPL11154

15 Samples

Download data: TXT