GEO DataSets

(Submitter supplied) The transcriptional activating and repressive functions performed by Trithorax and Polycomb group complexes, respectively, are critical for to maintain cellular fates in ontogeny and in cancer. Here we report that leukemias initiated by a Trithorax-related oncogene, MLL-AF9, depend upon the Polycomb Repressive Complex 2 (PRC2) to sustain a transformed cellular state. RNAi mediated suppression of PRC2 subunits is sufficient to inhibit proliferation of MLL-AF9 leukemias, with little impact on growth of non-transformed cells. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

9 Samples

Download data: CEL

(Submitter supplied) We sequenced mRNA from MLL-AF9 transformed Cdkn2ako murine LSK-cells with and without a functional Eed locus

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

2 Samples

Download data: TXT

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

Organism:

Mus musculus

Type:

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

Platforms:

GPL13112 GPL1261

23 Samples

Download data: CEL, WIG

(Submitter supplied) Chromatin immunoprecipitation (ChIP) for H3K27me3 followed by Solexa sequencing in WT and Ezh2-null leukemic cells from primary and secondary recipients.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

4 Samples

Download data: WIG

(Submitter supplied) We evaluated gene expression changes in secondary recipient murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of a homozygous conditional allele for Ezh2, a component of the Polycomb Repressive Complex2.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

9 Samples

Download data: CEL, TXT

(Submitter supplied) We evaluated gene expression changes in murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of homozygous conditional alleles for Ezh2 or Eed, both of which are components of the Polycomb Repressive Complex2.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

10 Samples

Download data: CEL, TXT

(Submitter supplied) Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

24 Samples

Download data: TXT

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

Organism:

Mus musculus

Type:

Expression profiling by array; Expression profiling by high throughput sequencing

Platforms:

GPL13112 GPL1261

55 Samples

Download data: CEL

(Submitter supplied) Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

4 Samples

Download data: TXT

(Submitter supplied) Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

12 Samples

Download data: TXT

(Submitter supplied) Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

15 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; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL19057 GPL17021

17 Samples

Download data: TXT

(Submitter supplied) Unlike clustered HOX genes, the role of non-clustered homeobox gene family members in hematopoiesis and leukemogenesis has not been extensively studied. Here we find that the Hematopoietically-expressed Homeobox gene, Hhex, is overexpressed in acute myeloid leukemia (AML) and is essential for the initiation and propagation of MLL-ENL induced AML, but dispensable for normal myelopoiesis, indicating a specific requirement for Hhex for leukemic growth. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: TXT

(Submitter supplied) Unlike clustered HOX genes, the role of non-clustered homeobox gene family members in hematopoiesis and leukemogenesis has not been extensively studied. Here we find that the Hematopoietically-expressed Homeobox gene, Hhex, is overexpressed in acute myeloid leukemia (AML) and is essential for the initiation and propagation of MLL-ENL induced AML, but dispensable for normal myelopoiesis, indicating a specific requirement for Hhex for leukemic growth. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL19057

9 Samples

Download data: TXT

(Submitter supplied) Polycomb activity is frequently altered in acute leukaemia through mutation or deletion of Polycomb Repressive Complex (PRC) components. Alterations in PRC-interacting factors such as the Core Binding Factor (CBF) complex should also affect leukemia biology, even if PRC composition is normal. We report that the acute myeloid leukemia (AML)-associated CBFβ-SMMHC fusion oncoprotein physically interacts with the PRC1 complex, and that these factors co-localize across the AML genome in a PRC2-independent manner. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL11154 GPL18573

18 Samples

Download data: BW

(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) Ezh2 and EZH1 are histone H3 lysine 27 (H3K27)-specific methyltransferases. Their hyperactive mutations and overexpression were found in cancer including various hematological malignancies. UNC1999 is a highly selective inhibitor for both enzymes. It suppresses H3K27 tri- and di-methylation globally and inhibits growth of MLL-rearranged acute leukemia. Here we performed ChIP-Seq to profile how UNC1999 affects distribution of H3K27me3 and its antagonizing H3K27ac in MLL-AF9-immortalized leukemia cells. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

11 Samples

Download data: WIG

(Submitter supplied) Ezh2 and EZH1 are histone H3 lysine 27 specific methyltransferase. Their hyperactive mutations and overexpression were found in cancer including various hematological malignancies. UNC1999 is a highly selective inhibitor for both enzymes. It suppresses H3K27 tri- and di-methylation globally and inhibits growth of MLL-rearranged acute leukemia cell lines. UNC2400, a di-methylated derivative of UNC1999, is employed an inactive analog compound for assessment of off-target effects. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

22 Samples

Download data: CEL

(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:

GPL17021 GPL18573 GPL9185

28 Samples

Download data: BW

(Submitter supplied) Acute myeloid leukemias (AMLs) with the NUP98-NSD1 or MLL gene rearrangement (MLL-r) share transcriptomic profiles featured with stemness-related gene signatures and display poor prognosis in the clinic. However, the molecular underpinnings of AML aggressiveness and stemness remain far from clear. Here, we report that the enzymatic activity of Polycomb Repressive Complex 2 (PRC2) is crucial for maintenance of tumorigenicity in NUP98-NSD1+ AML, consistent to its role in MLL-r AML. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9185

4 Samples

Download data: BW