GEO DataSets

(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:

GPL13112 GPL11154

27 Samples

Download data: BW, TXT

(Submitter supplied) Purpose: To characterize transcriptional changes associated with homozygous inactivation of Dot1l or Mll1 in MN1 driven AML Methods: We sequenced mRNA from murine LSK-cells transformed using forced expression of MN1 (MSCV-MN1-IRES-GFP), and transduced with Cre-vector to inactivate either Dot1l or Mll1. Cells were sorted for Cre-expression (pTomato fluorescent marker) or expression of an inert control vector. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

5 Samples

Download data: TXT

(Submitter supplied) Purpose: To characterize transcriptional changes associated with homozygous inactivation of Dot1l or Mll1 in MN1 driven AML Methods: We sequenced mRNA from murine LSK-cells transformed using forced expression of MN1 (MSCV-MN1-IRES-GFP), and transduced with Cre-vector to inactivate either Dot1l or Mll1. Cells were sorted for Cre-expression (pTomato fluorescent marker) or expression of an inert control vector. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: TXT

(Submitter supplied) Purpose: To characterize transcriptional changes associated with inhibition of Dot1l in 2 inv(16) patient AML samples Methods: We sequenced mRNA from patient samples that were exposed to 5 uM EPZ004777 or DMSO control for 7 days. Results: Inhibition of Dot1l leads to gene expression changes in genes related to cell growth and cell cycle.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: TXT

(Submitter supplied) Purpose: To characterize the genome-wide distribution of H3K79me2 in murine MN1 driven myeloid leukemia Methods: We performed Chip-seq for the H3K79me2 in leukemias isolated from moribund mice that had been injected with common myeloid progenitors (CMPs) transduced with MSCV-MN1-GFP Results: H3K79me2 is enriched at key loci that 1. are bound by MN1 in the data set of Heuser et al, (Cancer Cell. 2011 Jul 12;20(1):39-52.), 2. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: BW, XLSX

(Submitter supplied) Purpose: To characterize the genome-wide distribution of H3K79me2 in human leukemia cell lines treated with the Dot1l inhibitor EPZ004777 or control Methods: We performed Chip-seq for the H3K79me2 on the leukemia cell lines Mutz3, Loucy and Molm14 after 6 days in culture in the presence of 3uM EPZ004777 or DMSO control Results: H3K79me2 is completely erased from key target genes such as the HOXA cluster. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

6 Samples

Download data: BW

(Submitter supplied) Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known how mutant NPM1 (NPM1mut) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1mut AML. Using a CRISPR-Cas9 genome editing domain screen, we show NPM1mut AML to be exceptionally dependent on the menin binding site in MLL1. Pharmacological small-molecule inhibition of the menin-MLL protein interaction had profound anti-leukemic activity in human and murine models of NPM1mut AML in vitro and in vivo. Combined pharmacological inhibition of menin-MLL and DOT1L resulted in dramatic suppression of HOX and FLT3 expression, induction of differentiation, and superior activity against NPM1mut leukemia. Together, MLL1 and DOT1L are chromatin regulators that control HOX, MEIS1 and FLT3 expression and are therapeutic targets in NPM1mut AML. Combinatorial small-molecule inhibition has synergistic on target activity and constitutes a novel therapeutic concept for this common AML subtype.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

13 Samples

Download data: TXT

(Submitter supplied) To investigate whether co-expression of PBX3/MEIS1 can mimic that of MLL-AF9, HOXA9/MEIS1 or HOXA9/PBX3 in inducing leukemogenesis, we conducted in vivo mouse bone marrow transplantation (BMT) assays. Briefly, normal mouse bone marrow (BM) progenitor (i.e., lineage negative; Lin-) cells collected from B6.SJL (CD45.1) donor mice (CD45.1) were retrovirally co-transduced with MSCVneo-MLL-AF9+MSCV-PIG (MLL-AF9), MSCVneo-HOXA9+MSCV-PIG (HOXA9), MSCVneo-HOXA9+MSCV-PIG-MEIS1 (HOXA9+MEIS1), MSCVneo-HOXA9+MSCV-PIG-PBX3 (HOXA9+PBX3), MSCV-PIG-PBX3+MSCVneo-MEIS1 (PBX3+MEIS1), MSCVneo+MSCV-PIG-PBX3 (PBX3) , MSCVneo+MSCV-PIG-MEIS1 (MEIS1), or MSCVneo+MSCV-PIG (normal control; NC). more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

20 Samples

Download data: CEL

(Submitter supplied) The Polymerase Associated Factor (PAFc) complex is an epigenetic regulating complex that has been shown to to be important for Acute Myeloid Leukemias harboring an MLL chromosomal translocations, such as MLL-AF9 leukemias. This study describes the transcriptomic profiling of AML cells following genetic deletion of the PAFc subunit Cdc73.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: TXT

(Submitter supplied) Dysregulation of HOXA/B genes is a dominant mechanism of leukemic transformation.HOXB locus-associated long non-coding RNA (lncRNAs), HOXBLINC, regulates transcription of the anterior HOXB genes and plays a critical role in hematopoiesis development. Here, we show that HOXBLINC lncRNA is up-regulated in over 60% of patients with AML. Interestingly, AML patients with high HOXBLINC expression have a significantly shortened survival as compared to low HOXBLINC expressing patients. more...

Organism:

Mus musculus; Homo sapiens

Type:

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

5 related Platforms

40 Samples

Download data: BED, TXT

(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:

GPL18573 GPL19057

84 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) Using mouse and human models of NUP98-rearrranged leukemia, we demonstrate that inhibition of MLL-Menin impairs leukemogenic gene expression and disrupts chromatin binding of MLL1 and NUP98 fusion proteins at a critical subset of genes that is essential for sustaining the undifferentiated leukemia phenotype.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL19057

57 Samples

Download data: TXT

(Submitter supplied) Using mouse and human models of NUP98-rearrranged leukemia, we demonstrate that inhibition of MLL-Menin impairs leukemogenic gene expression and disrupts chromatin binding of MLL1 and NUP98 fusion proteins at a critical subset of genes that is essential for sustaining the undifferentiated leukemia phenotype.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

24 Samples

Download data: NARROWPEAK

(Submitter supplied) Using mouse and human models of NUP98-rearrranged leukemia, we demonstrate that inhibition of MLL-Menin impairs leukemogenic gene expression and disrupts chromatin binding of MLL1 and NUP98 fusion proteins at a critical subset of genes that is essential for sustaining the undifferentiated leukemia phenotype.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

3 Samples

Download data: NARROWPEAK

(Submitter supplied) OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX proteins, such as HOXA9, to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. To further resolve these mechanisms, we conducted a structure-function analysis of Meis1 and gene expression profiling, in the context of Hoxa9 leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the homeodomain of Meis1 is required for leukemogenic collaboration with Hoxa9. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6193

12 Samples

Download data: CEL, CHP

(Submitter supplied) Gene expression upon DOT1L inhibition, or Menin inhibition, or a combination of DOT1L and Menin inhibiting agents, was assessed in several MLL-rearranged human cell lines and a mouse model of MLL-AF9 leukemia. The goal of the study was to explore the mechanisms by which the EPZ0004777 and MI-2-2 chemicals collaborate to induce differentiation and cell death in MLL-AF4 and MLL-AF9 leukemias.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platforms:

GPL1261 GPL570

56 Samples

Download data: CEL

(Submitter supplied) The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations that involve the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in a murine MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3 and H3K36me3. Histone methylation patterns are highly abnormal on MLL-AF9 fusion target loci, defining a distinct epigenetic lesion involving H3K79. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11002 GPL10999 GPL13112

15 Samples

Download data: WIG

(Submitter supplied) MLL-fusions may induce leukemogenic gene expression programs by recruiting the histone H3K79 methyltransferase to MLL-target promoters. We evaluated gene expression changes after cre-mediated loss of Dot1l in leukemia cells obtained from mice injected with MLL-9 transformed lineage negative bone marrow cells.

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS4295

Platform:

GPL1261

26 Samples

Download data: CEL

Analysis of Mixed Lineage Leukemia (MLL)-AF9 leukemia cells after loss of Dot1l for up to 7 days. Loss of Dot1l leads to decreased growth, differentiation, and apoptosis of MLL-AF9 cells. Results provide insight into role of Dot1l in MLL-rearranged leukemia.

Organism:

Mus musculus

Type:

Expression profiling by array, count, 2 genotype/variation, 3 time sets

Platform:

GPL1261

Series:

GSE25911

26 Samples

Download data: CEL

(Submitter supplied) DNA methyltransferase 3A (DNMT3A) is frequently mutated in hematological cancers; however, the underlying oncogenic mechanism remains elusive. Here, we report that DNMT3A mutational hotspot at Arg882 (DNMT3A R882H) cooperates with NRAS mutation to transform hematopoietic stem/progenitor cells and induce acute leukemia development. Mechanistically, DNMT3A R882H directly binds to and potentiates transactivation of stemness genes critical for leukemogenicity including Meis1, Mn1 and Hoxa gene cluster. more...

Organism:

Mus musculus

Type:

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

Platforms:

GPL1261 GPL13112 GPL17400

46 Samples

Download data: BEDGRAPH, BIGBED, CEL