GEO DataSets

(Submitter supplied) MLL-r cell lines KOPN-8 and NOMO-1 were cultured with pinometostat to derive treatment emergent resistant pools. RNA sequencing was performed on the resistant pools to generate hypotheses around mechanisms of resistance

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

24 Samples

Download data: XLSX

(Submitter supplied) MLL-rearranged (MLL-r) leukemia, a particularly intractable disease, depends on DOT1L-mediated H3K79 methylation. Depletion of this transcriptionally activating mark by DOT1L loss-of-function or high concentrations of highly-specific inhibitor pinometostat (≥1 mM EPZ5676) leads to the downregulation of HOXA9 and MEIS1, and consequent reduction leukemia survival. . Yet, some MLL-r cell lines are inexplicably susceptible to low-dose pinometostat, below the threshold for downregulating these canonical oncogenic drivers. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL18573

22 Samples

Download data: BED, BEDGRAPH, BIGWIG, BW, FPKM_TRACKING

(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) 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

Platforms:

GPL13112 GPL14761 GPL1261

44 Samples

Download data: BW, CEL, TDF

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

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

14 Samples

Download data: IDAT

(Submitter supplied) Gene expression analysis of two MLL-r leukaemia cell lines (SM6p2 and SM6p3) and the parental PER-485 MLL-rearranged leukaemia cell line they were derived from by continuous culturing in CCI-006. SM6p2 and SM6p3 thereby developed induced resistance against the compound. The aim of this experiment was to identify any gene expression changes in SM6p2 and SM6p3 cells induced by continuous culturing in CCI-006, thereby potentially providing insight into the mechanisms of primary and induced resistance of MLL-rearranged leukaemia cell lines against the cytotoxic compound CCI-006.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

8 Samples

Download data: IDAT, TXT

(Submitter supplied) A phenotypic cell-based high-throughput screen identified a novel small molecule, CCI-006 with selective cytotoxic activity against MLL-rearranged leukaemia cell lines. The aim of this experiment was to identify the mechanism of action of CCI-006 by investigating the gene expression changes induced in a MLL-rearranged leukaemia cell line following a short incubation with the compound.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

6 Samples

Download data: IDAT, TXT

(Submitter supplied) In this study, we identify MBNL1 as a unique molecular vulnerability across MLL-rearranged leukemias. Through transcriptomic profiling and novel splicing analyses of MLL-rearranged leukemia cell lines following shRNA knockdown of MBNL1, we show that MBNL1 regulates alternative splicing (predominantly intron retention) of genes essential to MLL-rearranged leukemogenesis, such as DOT1L and SETD1A.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

28 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:

Mus musculus; Homo sapiens

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) 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) The purpose of this study is to investigate the transcriptional programs as it relates to disease latency initiated by different MLL fusion proteins, including: MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 and MLL-ENL. Leukemia cell lines were established by transforming kit+ mouse bone marrow cells with retroviruses coding MLL-AF1p, MLL-AF6, MLL-Gas7, MLL-AF9 or MLL-ENL. At early phase after the cell lines were established, cells growing at exponential phase (cell density at 0.5~1x106/ml) were harvested for RNA extraction and sequencing purpose.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

12 Samples

Download data: TXT

(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:

Mus musculus; Homo sapiens

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