GEO DataSets

(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

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: BEDGRAPH

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: BIGBED

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

13 Samples

Download data: BEDGRAPH

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

10 Samples

Download data: CEL

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (i.e., DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

12 Samples

Download data: CEL

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

Organism:

Homo sapiens

Type:

Methylation profiling by array; Methylation profiling by high throughput sequencing

Platforms:

GPL13534 GPL11154

70 Samples

Download data: TXT

(Submitter supplied) Whole genome bisulphite sequencing of 2 human cancer cell line samples. One cell line harbours a heterozygous mutation in the DNA methyl-transferase DNMT3a, a common alteration observed in AML patients. The main goal is to find the differentially methylated regions (DMR) at genome-wide level between the mutant and a wild-type cell lines to elucidate the effect of the mutation and the implication in leukomogenesis.

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

2 Samples

Download data: TXT

(Submitter supplied) Genome-scale DNA methylation profiling using the Infinium DNA methylation BeadChip platform and samples from acute myeloid leukemia patients screened for their mutation status of DNMT3a, a frequent aberration in AML.

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL13534

68 Samples

Download data: TXT

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

Organism:

Homo sapiens

Type:

Third-party reanalysis; Methylation profiling by high throughput sequencing

Platform:

GPL11154

126 Samples

Download data: TXT

(Submitter supplied) Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. more...

Organism:

Mus musculus; Homo sapiens

Type:

Methylation profiling by high throughput sequencing; Third-party reanalysis

Platform:

GPL11154

7 Samples

Download data: BED, TXT

(Submitter supplied) Aberrant DNA methylation of gene promoters is a hallmark of AML. To define how cytosine methylation is redistributed in AML more precisely we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

119 Samples

Download data: TXT

(Submitter supplied) DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies. We report that DNMT3A mutational ‘hotspot’ at Arg882 (i.e., DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. Mechanistically, DNMT3A-R882H induced DNA hypomethylation facilitates gene enhancer/promoter activation. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

4 Samples

Download data: CEL

(Submitter supplied) Mutation of DNA methyltransferase 3A at arginine 882 (DNMT3AR882mut) is prevalent in various hematological cancers. DNMT3AR882mut was recently shown to carry partially defective, dominant-negative or gain-of-function activities under different in vitro contexts. However, the causal roles for such a multifaceted effect of DNMT3AR882mut on leukemogenesis remain undefined. Here we report TF-1 leukemia cells as a robust system for modeling DNMT3AR882mut-dependent cell transformation phenotypes and for performing structure-function relationship studies of DNMT3AR882mut. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

35 Samples

Download data: TXT

(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