GEO DataSets

(Submitter supplied) The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens, we identified selective and pan-histone deacetylase inhibitors (HDACis) as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, we dissected the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstituted the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: MTX, TSV

(Submitter supplied) The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens, we identified selective and pan-histone deacetylase inhibitors (HDACis) as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, we dissected the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstituted the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

9 Samples

Download data: TXT

(Submitter supplied) The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens, we identified selective and pan-histone deacetylase inhibitors (HDACis) as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, we dissected the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstituted the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: MTX, TSV

(Submitter supplied) The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens, we identified selective and pan-histone deacetylase inhibitors (HDACis) as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, we dissected the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstituted the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 protein. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

18 Samples

Download data: BIGWIG

(Submitter supplied) The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens, we identified selective and pan-histone deacetylase inhibitors (HDACis) as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, we dissected the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstituted the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

4 Samples

Download data: MTX, TSV

(Submitter supplied) Selective and pan-histone deacetylase inhibitors (HDACis) emerged at the intersection of these approaches. HDACis suppress EVI1 expression and preferentially impair leukemia proliferation in 3q26 AML compared to other leukemia subtypes in multiple preclinical models. To understand this mechanism of action, we dissected the expression dynamics of the bone marrow leukemia cells of patients treated with hit list compounds, reconstituted with the chromatin-associated co-transcriptional complex of EVI1 by rapid immunoprecipitation mass spectrometry (RIME) in human 3q26 AML models; we focused on the role of the proliferation-associated 2G4 (PA2G4) protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

36 Samples

Download data: TXT

(Submitter supplied) Ecotropic virus integration site 1 (EVI1), whose overexpression characterizes a particularly aggressive subtype of acute myeloid leukemia (AML), enhanced anti-leukemic activities of all-trans retinoic acid (atRA) in cell lines and patient samples. However, the drivers of leukemia formation, therapy resistance, and relapse are leukemic stem cells (LSCs), whose properties were hardly reflected in these experimental setups. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21493

10 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) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

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

Platforms:

GPL24676 GPL16791

37 Samples

Download data: BIGWIG, NARROWPEAK, SF

(Submitter supplied) Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable with current chemotherapy regimens. Insight into the mechanism by which EVI1 drives myeloid transformation is needed to target EVI1 in those leukemias. Here we demonstrate recurrent interaction of CTBP1/2 with a unique PLDLS motif in EVI1, which is indispensable for leukemic transformation of 3q26/MECOM rearranged AML. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL24676 GPL16791

31 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) Chromosomal rearrangements involving EVI1 (MECOM) define a subtype of acute myeloid leukemia (AML) that is associated with a two-year survival rate of <10%. Gene regulatory functions of EVI1 are largely elusive and no targeted therapeutics exist. We developed experimentally tractable murine and human leukemia models that recapitulate phenotypic and transcriptional features of EVI1-rearranged AML and enable large-scale loss-of-function screens. more...

Organism:

Homo sapiens; Mus musculus

Type:

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

4 related Platforms

38 Samples

Download data: BIGWIG, TXT

(Submitter supplied) Determine the differences in gene expression profiles of MV-4-11 AML cells treated with HDAC1/2-selective inhibition, azacitidine, or the combination of the two agents. Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15207

4 Samples

Download data: CEL

(Submitter supplied) The BET (bromodomain and extra terminal) protein family members including BRD4 bind to acetylated lysines on histones and regulate the expression of important oncogenes, e.g., MYC and BCL2. Here we demonstrate the sensitizing effects of the histone hyperacetylation inducing pan-histone deacetylase inhibitor (HDI) panobinostat (PS) on human AML blast progenitor cells (BPCs) to the BET protein inhibitor JQ1. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

2 Samples

Download data: CEL

(Submitter supplied) Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS5809

Platform:

GPL11532

8 Samples

Download data: CEL

Analysis of myeloid cell line U937 overexpressing ecotropic viral integration site 1 (EVI1) and cultured in the presence of antileukemic drug etoposide. Results provide insight into molecular mechanisms through which EVI1 confers resistance to drugs used in myeloid leukemia therapy.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 agent, 2 protocol sets

Platform:

GPL11532

Series:

GSE66660

8 Samples

Download data: CEL

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

Organism:

Mus musculus; Homo sapiens

Type:

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

Platforms:

GPL16791 GPL19057

10 Samples

Download data: BIGWIG

(Submitter supplied) Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 at MECOM drive inv(3)/t(3;3) myeloid leukemias and revealed MECOM germline mutations in patients with MECOM-associated bone marrow failure syndromes. Here we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 which is frequently present in inv(3)/t(3;3) AML and directly contributes to leukemic transformation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

2 Samples

Download data: TXT, XLSX