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Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [Bisulfite-Seq]

ABSTRACT: Acute myeloid leukemia (AML) is a fatal hematological malignancy for most patients, and DNA methyltransferase 3A (DNMT3A) mutations occur in about 30-35% of AML patients. We show graphdiyne oxide (GDYO), a member of two-dimensional carbon nanomaterials3, demonstrates an anti-leukemia effect in vitro and in vivo against AML cells with DNMT3A mutation specifically. Here, we used reduced representation bisulfite sequencing (RRBS) to depict DNA methylome of AML cells with or without GDYO treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190873 | GEO | 2022/08/23

REPOSITORIES: GEO

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Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [RNA-Seq]

Project description:Acute myeloid leukemia (AML) is a fatal hematological malignancy for most patients, and DNA methyltransferase 3A (DNMT3A) mutations occur in about 30-35% of AML patients. We show graphdiyne oxide (GDYO), a member of two-dimensional carbon nanomaterials3, demonstrates an anti-leukemia effect in vitro and in vivo against AML cells with DNMT3A mutation specifically. Here, we used RNA-seq to depict transcriptome of AML cells with or without GDYO treatment.

2022-08-23 | GSE190871 | GEO

Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells

Project description:Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells

| PRJNA788776 | ENA

Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [Bisulfite-Seq]

Project description:Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [Bisulfite-Seq]

| PRJNA788779 | ENA

Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [RNA-Seq]

Project description:Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells [RNA-Seq]

| PRJNA788781 | ENA

Graphdiyne oxide nanosheets display anti-leukemia efficacy specifically against DNMT3A-mutant AML cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-23 | GSE190874 | GEO

Hotspot DNMT3A and IDH1/2 Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy

Project description:DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 & 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7-23% of acute myeloid leukemia (AML). Here, we investigated whether hotspot mutations in these genes encode neoantigens that can be targeted by immunotherapy. Five EBV-B cell lines expressing common HLA class I alleles were transduced with a minigene construct containing mutations that often occur in DNMT3A or IDH1/2. Peptides eluted from HLA class I alleles on these EBV-B cell lines were analyzed by tandem mass spec-trometry. We identified an HLA-A*01:01-binding DNMT3AR882H peptide and HLA-B*07:02-binding IDH2R140Q peptide, for which we searched for specific T cells in healthy individuals using pep-tide-HLA tetramers. Various T-cell clones were isolated showing specific reactivity against cell lines transduced with full-length DNMT3AR882H or IDH2R140Q genes, while cell lines transduced with wildtype genes were not recognized. One T-cell clone for DNMT3AR882H also reacted against patient AML cells with the mutation, while AML cells without the mutation were not recognized, thereby validating surface presentation of a DNMT3AR882H neoantigen that can potentially be targeted on HLA-A*01:01 positive AML by immunotherapy.

2024-06-23 | PXD050560 | Pride

Differential genomic-methylation profile of EOL-1 cells transduced with WT/mutant-DNMT3A

Project description:DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Here we wished to perform the differential genomic-methylation profile in EOL-1 cells over-expressed with DNMT3A-Arg882Cys(R882C) and DNMT3A-Ser714Cys (S714C) mutations including DNMT3A-WT and vector. Results: Differential genomic-methylation assess identified both hypo- and hypermethylation features in different regions throughout the whole genome of DNMT3A mutants-transduced EOL-1 cells.

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Differential genomic-methylation profile of U937 cells transduced with WT/mutant-DNMT3A

Project description:DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Despite the current progress of functional role of DNMT3A mutations, the molecular pathogenesis of myeloid malignancies remains poorly understood. The mechanisms of AML transformation and functional role of DNMT3A mutations through its target genes in the leukemogenesis remain to be explored. Here we wished to perform the differential genomic-methylation profile in U937 cells over-expressed with DNMT3A-Arg882His/Cys (R882H/C) mutations including DNMT3A-WT and vector using Illumina MethylationEPIC BeadChip microarray. Results: Differential genomic-methylation assess identified both hypo- and hypermethylation features in different regions throughout the whole genome of DNMT3A mutants-transduced U937 cells.

2017-12-01 | GSE90933 | GEO

Differential gene expression profile in U937 cells transduced with WT/mutant-DNMT3A

Project description:DNA methyltransferase 3A (DNMT3A) gene is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Despite the current progress of functional role of DNMT3A mutations, the molecular pathogenesis of myeloid malignancies remains poorly understood. The mechanisms of AML transformation and functional role of DNMT3A mutations through its target genes in the leukemogenesis remain to be explored. Here we wished to perform the differential gene expression profile in U937 cells over-expressed with DNMT3A-Arg882His/Cys (R882H/C) mutations including DNMT3A-WT and vector. Results: Gene expression profiling analysis revealed aberrant expression of several cell-cycle and apoptosis-related genes in U937 cells transduced with mutant DNMT3A compared to WT- or vector control.

2017-12-01 | GSE90931 | GEO

Transcription profiling of acute monocytic leukemia (AML-M5) patients with DNMT3A mutations

Project description:To understand the pathogenesis of DNMT3A in acute monocytic leukemia (AML-M5), we identified genes that are expressed differently in leukemia cells from AML-M5 patients collected at diagnosis with DNMT3A mutations (6 cases) compared to those without the mutations (4 cases). Differences of expression level were observed in 889 out of 20,723 (4.3%) annotated genes by using Affymetrix microarray with 469 genes upregulated and 420 genes downregulated. Leukemia cells in bone marrow of acute monocytic leukemia patients were collected at diagnosis for RNA extraction and hybridization on Affymetrix microarrays. 6 cases of AML-M5 samples with DNMT3A mutations and 4 cases of AML-M5 samples wihtout DNMT3A mutations were used.

2011-02-12 | E-GEOD-27187 | biostudies-arrayexpress

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