GEO DataSets

(Submitter supplied) We hypothesized that DNA methylation distributes into specific patterns in cancer cells, which reflect critical biological differences. We therefore examined the methylation profiles of 344 patients with acute myeloid leukemia (AML). Clustering of these patients by methylation data segregated patients into 16 groups. Five of these groups defined new AML subtypes that shared no other known feature. In addition, DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11 and PML-RARA leukemia entities are associated with specific methylation profiles. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL6604

352 Samples

Download data: PAIR

(Submitter supplied) Mutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5-14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry two mutations (CEBPAdouble-mut), usually biallelic, while single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high performance liquid chromatography and nucleotide sequencing we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases, i.e. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

526 Samples

Download data: CEL

(Submitter supplied) The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA-sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared to wildtype cases include genes involved in MDS pathogenesis (ASXL1, CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7, SLC25A37) and RNA splicing/processing (PRPF8, HNRNPD). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

17 Samples

Download data: TXT

(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) Purpose: Identify new targets in EVI1-Positive Acute Myeloid Leukemia Methods: Treatment with cyclocreatine of EVI1-driven AML cell lines TF-1, UT-7 and UCSD-AML1. Cyclocreatine was purchased from Sigma-Aldrich (Sigma). TF-1, UT-7 and UCSD-AML1 cells were treated in quadruplicate with either vehicle or 3 mM cyclocreatine for 24 hours. Total RNA was extracted and profiled by RNA sequencing (HiSeq, Illumina) at BioMicroCenter from Massachusetts Institute of Technology (Cambridge, MA, USA). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

24 Samples

Download data: TXT

(Submitter supplied) Background: The transcription factor EVI1 regulates cellular proliferation, differentiation, and apoptosis, and contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

20 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) We studied the variations of mRNA amounts after Flag-EVI1, Flag-EVI1Δ324, or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

12 Samples

Download data: CEL

(Submitter supplied) The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS5613

Platform:

GPL570

12 Samples

Download data: CEL

(Submitter supplied) To investigate whether and how expression of the oncogenic transcription factor EVI1 influences gene regulation by phorbol esters and vice versa, the human myeloid cell line U937 was transduced with an EVI1 expression vector or empty vector as a control. Cells were treated with 12-Otetradecanoylphorbol 13-acetate (TPA) or its solvent ethanol as a control. RNA was extracted and subjected to gene expression microarray analysis.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

12 Samples

Download data: CEL

(Submitter supplied) The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS5614

Platform:

GPL570

12 Samples

Download data: CEL

Analysis of EVI1-overexpressing HL60 myeloid cells treated with ATRA. EVI1 overexpression is associated with poor prognosis in myeloid leukemias; ATRA is a myeloid differentiation inducing agent. Results provide insight into the potential interplay between EVI1 and ATRA in myeloid cells.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 agent, 2 genotype/variation sets

Platform:

GPL570

Series:

GSE66837

12 Samples

Download data: CEL

Analysis of EVI1-overexpressing U937 myeloid cells treated with ATRA. EVI1 overexpression is associated with poor prognosis in myeloid leukemias; ATRA is a myeloid differentiation inducing agent. Results provide insight into the potential interplay between EVI1 and ATRA in myeloid cells.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 agent, 2 genotype/variation sets

Platform:

GPL570

Series:

GSE66854

12 Samples

Download data: CEL

(Submitter supplied) SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in MDS. We have performed a comprehensive analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in bone marrow CD34+ cells of a large group of 82 MDS patients. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

131 Samples

Download data: TXT

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

Organism:

Homo sapiens; Mus musculus

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

(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:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

8 Samples

Download data: BIGWIG

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

Organism:

Mus musculus; Homo sapiens

Type:

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

Platforms:

GPL24676 GPL21103 GPL16791

19 Samples

Download data: RESULTS, TXT

(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:

GPL21103

12 Samples

Download data: RESULTS