Azacitidine treated AML cells reveals highly variable cell surface proteome remodeling [Affymetrix]
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ABSTRACT:
PROVIDER: PRJNA507808 | ENA |
REPOSITORIES: ENA
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Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell surface proteome. Untreated AML cell lines showed substantial overlap at all three omics level; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly upregulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatmentled to diverse effects at the individual gene and protein level but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, the potential therapeutic strategies for AML in combinations with AZA are discussed.
2018-12-01 | GSE123207 | GEO
Project description:Azacitidine treated AML cells reveals highly variable cell surface proteome remodeling
| PRJNA507806 | ENA
Project description:Azacitidine treated AML cells reveals highly variable cell surface proteome remodeling [Illumina]
| PRJNA507643 | ENA
Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell surface proteome. Untreated AML cell lines showed substantial overlap at all three omics level; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly upregulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatmentled to diverse effects at the individual gene and protein level but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, the potential therapeutic strategies for AML in combinations with AZA are discussed.
2018-11-30 | GSE123140 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-01 | GSE123211 | GEO
Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell surface proteome. Untreated AML cell lines showed substantial overlap at all three omics level; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatment led to diverse effects at the individual gene and protein level but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, we discuss potential therapeutic strategies for AML in combinations with AZA.
2018-10-07 | MSV000083006 | MassIVE
Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor widely used to treat MDS and AML, yet the impact of AZA on the cell-surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell-surface proteome. Untreated AML cell lines showed substantial overlap at all three omics levels; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteome analysis found no commonly regulated proteins. Gene set enrichment analysis of differentially regulated RNA and surface proteins showed a decrease in metabolic pathways and an increase in immune defense response pathways. As such, AZA treatment led to diverse effects at the individual gene and protein levels but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, we discuss potential therapeutic strategies for AML in combination with AZA.
| S-EPMC6329958 | biostudies-literature
Project description:Campylobacter isolates variable, Sweden
| PRJEB40817 | ENA
Project description:Transcriptomic profiling was performed on six cell lines derived from infants with KMT2A-rearranged ALL following treatment with two hypomethylating drugs (azacitidine and decitabine) administered at low doses for 72 hours in vitro. We identified changes in gene expression following treatment with hypomethylating agents, with decitabine exerting a greater effect than azacitidine.
2022-12-31 | GSE212591 | GEO
Project description:Biomarker study for a phase 1, Open-Label, multicenter trial of azacitidine (CC-486) plus R-CHOP in subjects with high-risk previously untreated diffuse large B-cell lymphoma
2022-06-29 | GSE157302 | GEO