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| Status |
Public on Dec 01, 2018 |
| Title |
Azacitidine treated AML cells reveals highly variable cell surface proteome remodeling [Affymetrix] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
To study the effects of AZA treatment on the regulation of DNA methylation, each of the four cell lines was treated with AZA (0.5 μM) for 3 days, followed by a four-day drug holiday
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| Contributor(s) |
Leung KK, Nguyen A, Shi T, Tang L, Ni X, Escoubet L, MacBeth KJ, DiMartino J, Wells JA |
| Citation(s) |
30584089 |
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| Submission date |
Nov 30, 2018 |
| Last update date |
May 06, 2020 |
| Contact name |
Samuel Danziger |
| E-mail(s) |
sdanziger@celgene.com
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| Organization name |
Celgene
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| Street address |
10300 Campus Point Dr
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE123211 |
Azacitidine treated AML cells reveals highly variable cell surface proteome remodeling |
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| Relations |
| BioProject |
PRJNA507808 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123207_RAW.tar |
82.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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