GEO DataSets

(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) 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) Here we used Illumina NGS for high-throughput profiling of the DNA methylome in two human colon cancer derived cell lines, two human normal bone marrow CD34+ controls and in five human Acutre Myeloid Leukeima patient samples. These data can be used to determine the CpG cytosine methylation pattern at base pair resolution in each sample and to determine differentially methylated cytosines and regions between samples

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platforms:

GPL10999 GPL11154

19 Samples

Download data: TXT

(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:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Methylation profiling by high throughput sequencing

Platform:

GPL13112

54 Samples

Download data: TXT

(Submitter supplied) Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH. Functional studies have shown these mutations contribute to transformation, although how these mutations impact the response to epigenetic therapies is not fully delineated. Here we show AMLs with TET2/IDH2 mutations combined with FLT3ITD mutations are specifically sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

19 Samples

Download data: TXT

(Submitter supplied) Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH. Functional studies have shown these mutations contribute to transformation, although how these mutations impact the response to epigenetic therapies is not fully delineated. Here we show AMLs with TET2/IDH2 mutations combined with FLT3ITD mutations are specifically sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL13112

35 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

102 Samples

Download data

(Submitter supplied) Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human acute myeloid leukemia (AML) cases with a 5-year overall survival of approximately 30%. In CN-AML with poorer prognosis, mutations in the de novo DNA methyltransferase (DNMT3A) and the FMS-like tyrosine kinase 3 (Flt3) commonly co-occur (1-3). We demonstrate that mice with Flt3-internal-tandem duplication (Flt3ITD) and inducible deletion of Dnmt3a spontaneously develop a rapidly-lethal, completely-penetrant, and transplantable AML of normal karyotype. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

96 Samples

Download data: TXT

(Submitter supplied) Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human acute myeloid leukemia (AML) cases with a 5-year overall survival of approximately 30%. In CN-AML with poorer prognosis, mutations in the de novo DNA methyltransferase (DNMT3A) and the FMS-like tyrosine kinase 3 (Flt3) commonly co-occur (1-3). We demonstrate that mice with Flt3-internal-tandem duplication (Flt3ITD) and inducible deletion of Dnmt3a spontaneously develop a rapidly-lethal, completely-penetrant, and transplantable AML of normal karyotype. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: TXT

(Submitter supplied) Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human acute myeloid leukemia (AML) cases with a 5-year overall survival of approximately 30%. In CN-AML with poorer prognosis, mutations in the de novo DNA methyltransferase (DNMT3A) and the FMS-like tyrosine kinase 3 (Flt3) commonly co-occur (1-3). We demonstrate that mice with Flt3-internal-tandem duplication (Flt3ITD) and inducible deletion of Dnmt3a spontaneously develop a rapidly-lethal, completely-penetrant, and transplantable AML of normal karyotype. more...

Organism:

Mus musculus; Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platforms:

GPL13112 GPL11154

44 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) DNA methyltransferases DNMT3A- and DNMT3B-mediated de novo DNA methylation critically regulates epigenomic and transcriptomic patterning during development. The hotspot DNMT3A mutations at the site of Arg822 (R882) promote macro-oligomer formation, leading to aberrant DNA methylation that in turn contributes to pathogenesis of acute myeloid leukemia (AML). However, the molecular basis underlying the hotspot mutation-induced functional mis-regulation of DNMT3A remains unclear. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL21145

32 Samples

Download data: IDAT, TXT