GEO DataSets

(Submitter supplied) Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and catalytic activity of DOT1L are required for MLL-rearranged leukemia. We evaluated gene expression changes after inhibition of AHD in leukemia cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

6 Samples

Download data: XLSX

(Submitter supplied) ENL is required for expression of MLL1-target genes as well as the aberrant gene expression in MLL1-r leukemia. We investigated the gene expression changes after selective chemical knockout of ENL in leukemia cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

6 Samples

Download data: TXT

(Submitter supplied) MLL-fusions are potent oncogenes that initiate aggressive forms of acute leukemia. As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. Notably, interference with MLL-fusion cofactors like DOT1L is an emerging therapeutic strategy in this disease. Here we identify the histone H2B E3 ubiquitin ligase RNF20 as an additional requirement for MLL-fusion-mediated leukemogenesis. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: TXT

(Submitter supplied) We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array; Genome binding/occupancy profiling by genome tiling array

Platforms:

GPL5082 GPL5811 GPL8321

49 Samples

Download data: BAR, BED, CEL

(Submitter supplied) We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by genome tiling array

Platform:

GPL5811

1 Sample

Download data: BAR, BED, BPMAP, CEL

(Submitter supplied) We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by genome tiling array

Platform:

GPL5811

2 Samples

Download data: BAR, BED, BPMAP, CEL

(Submitter supplied) We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by genome tiling array

Platform:

GPL5082

3 Samples

Download data: BAR, BED, BPMAP, CEL

(Submitter supplied) We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

4 Samples

Download data: CEL

(Submitter supplied) We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Immunophenotypic and gene expression analysis of the ALL cells demonstrated bone marrow replacement with B-precursor cells which express a gene expression profile that has significant overlap with profiles in human MLL-rearranged ALL. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

39 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 GPL13112 GPL10999

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) The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemias are consistently poor prognosis. One of the most common translocation partners is AF9 (a.k.a. MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites, and present the NMR solution structure of a DOT1L-AF9 complex. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16417

6 Samples

Download data: TXT

(Submitter supplied) Purpose: The chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene have been extensively characterized as a potent oncogenic driver on the molecular and mechanistic level in acute lymphoblastic (ALL) and acute myeloid (AML) leukemia. For its oncogenic function the MLL fusion protein is hijacking the the multi enzyme super elongation complex (SEC) leading to elevated expression of MLL target genes (e.g. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

305 Samples

Download data: TSV

(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:

Mus musculus; Homo sapiens

Type:

Expression profiling by array

Platforms:

GPL1261 GPL570

56 Samples

Download data: CEL

(Submitter supplied) Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the Mixed Lineage Leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor prognosis leukemias. Here we find that MLL-AF4 occupies a subset of unmethylated CG-enriched genes in combination with its cofactors Menin/LEDGF and ENL. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL16791 GPL11154 GPL18573

59 Samples

Download data: BED, BW, TXT

(Submitter supplied) In MLL-rearranged (MLLr) leukemias the N terminal part of the MLL gene can be fused to over 60 different partner genes. Here, we investigate the genome wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and their epigenetic signatures in order to define a core set of MLLr targets. We uncover both common as well as specific MLL-AF9 and MLL-AF4 target genes, which are all marked by H3K79me2, H3K27ac, and H3K4me3. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL11154 GPL10999

24 Samples

Download data: BEDGRAPH, WIG

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

Organism:

Homo sapiens; Mus musculus

Type:

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

4 related Platforms

10 Samples

Download data: CEL, WIG

(Submitter supplied) The MLL gene on chromosome 11 fuses to the AF6 gene on chromosome 6 in a balanced chromosomal translocation that is characetristic of certain adult and pediatric human leukemias. We established a murine leukemia model of MLL-AF6 using the retroviral MLL-AF6 contruct in a bone marrow transplantation system. The ML2 human MLL-AF6 positive leukemia cell line was used for gene expression profiling to assess the transctiptional profile in MLL-AF6 leukemias.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

1 Sample

Download data: CEL

(Submitter supplied) The MLL gene on chromosome 11 fuses to the AF6 gene on chromosome 6 in a balanced chromosomal translocation that is characetristic of certain adult and pediatric human leukemias. We established a murine leukemia model of MLL-AF6 using the retroviral MLL-AF6 contruct in a bone marrow transplantation system.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

3 Samples

Download data: CEL