GEO DataSets

(Submitter supplied) We investigated the role of the transcriptional regulators Id2 and E2-2 (encoded by Tcf4) in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by a Tet-off inducible MLL-AF9 allele co-expressed with oncogenic NRASG12D, we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in MLL-AF9 AML cells results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: TXT

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

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

32 Samples

Download data

(Submitter supplied) We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by tet-regulated MLL-AF9 co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in Tet-Off MLL-AF9 AML cells in vitro partially phenocopies MLL-AF9 depletion and results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

14 Samples

Download data: TXT

(Submitter supplied) We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an Id2/GFP-reporter mouse model of MLL-AF9-driven AML, we showed that Id2 is expressed heterogeneously across the leukemic population. Moreover, differential expression of Id2 and the stemness marker Kit defines subsets of AML cells with different leukemogenic properties with lower levels of Id2 associated with enrichment in leukemia stem cell potential. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

12 Samples

Download data: TXT

(Submitter supplied) ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

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

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Expression profiling by array

Platforms:

GPL13112 GPL6246

41 Samples

Download data: CEL

(Submitter supplied) To address the impact of cellular origin on AML, we generated an inducible transgenic mouse model for MLL-AF9 driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSCs) in vitro resulted in unprecedented clonogenic growth and expression of genes involved in migration and invasion. In vivo, some LT-HSC-derived AMLs were particularly aggressive with extensive tissue infiltration, chemo-resistance and expression of genes related to epithelial-mesenchymal transition (EMT) in solid cancers. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

15 Samples

Download data: TXT

(Submitter supplied) To address the impact of cellular origin on AML, we generated an inducible transgenic mouse model for MLL-AF9 driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSCs) in vitro resulted in unprecedented clonogenic growth and expression of genes involved in migration and invasion. In vivo, some LT-HSC-derived AMLs were particularly aggressive with extensive tissue infiltration, chemo-resistance and expression of genes related to epithelial-mesenchymal transition (EMT) in solid cancers. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

26 Samples

Download data: CEL

(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:

GPL10999 GPL11154

24 Samples

Download data: BEDGRAPH, WIG

(Submitter supplied) Leukemias derived from the MLL-AF9 rearrangement rely on deranged transcriptional networks. ZNF521, a transcription co-factor implicated in the control of hematopoiesis, has been proposed to sustain leukemic transformation in collaboration with other oncogenes. We demonstrate here that ZNF521 mRNA levels correlate with specific genetic aberrations: in particular, the highest expression is observed in AMLs bearing MLL rearrangements, while the lowest is detected in AMLs with FLT3-ITD, NPM1 or CEBPα double mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL23126

10 Samples

Download data: CEL

(Submitter supplied) MLL-AF9 expression in normal human umbilical cord blood CD34+ cells leads to long-term proliferation of a myeloid progenitor cell with leukemogenic potential. Expression of a Core Binding Factor leukemia fusion (AML1-ETO or CBFbeta-SMMHC) in human CD34+ cells results in self-renewal of primitive progenitor cells with multilineage potential and stem cell ability, but these cells do not induce leukemia in immunodeficient mice. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

18 Samples

Download data: CEL

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

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platforms:

GPL5175 GPL6246

48 Samples

Download data: CEL

(Submitter supplied) To identify such targets of leukemia-related miRNAs such as miR-196b, we conducted Affymetrix gene arrays of leukemic BM samples from 24 mice including 9 primary (including 3 each of negative control, MLL-AF9, and miR-196b+MLL-AF9) and 15 secondary (including 3 negative control, 6 MLL-AF9, and 6 miR-196b+MLL-AF9) recipient mice

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

24 Samples

Download data: CEL

(Submitter supplied) Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13781

65 Samples

Download data: TXT

(Submitter supplied) MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling of human AML and normal control samples, we found that ALOX5 is especially down-regulated in MLL-rearranged AML. Our colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

4 Samples

Download data: TXT

(Submitter supplied) To identify potential target genes of leukemia-related miRNAs such as miR-196b and miR-150 in human MLL-associated leukemia, we performed Affymetrix Human Exon 1.0 ST array assay of 15 human MLL-associated samples and 9 human normal bone marrow (including 3 each of CD34+, CD33+, and MNC) cell samples.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

24 Samples

Download data: CEL

(Submitter supplied) Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

93 Samples

Download data: CEL

(Submitter supplied) The aim of the study was to investigate the role of TGIF1 in MLL-AF9 transformed cells Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are prominent downstream effectors of oncogenic fusion proteins generated from translocations involving the mixed lineage leukemia (MLL) gene. A particular well-characterized member of this protein family is MEIS1, which together with HOXA proteins, orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). more...

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS5456

Platform:

GPL6246

6 Samples

Download data: CEL, TXT

(Submitter supplied) Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are prominent downstream effectors of oncogenic fusion proteins generated from translocations involving the mixed lineage leukemia (MLL) gene. A particular well-characterized member of this protein family is MEIS1, which together with HOXA proteins, orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL13112 GPL11002

9 Samples

Download data: BW, TXT