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PXD011298

PXD011298 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMulti-omics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell surface proteome
DescriptionMyelodysplastic 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.
HostingRepositoryMassIVE
AnnounceDate2018-12-15
AnnouncementXMLSubmission_2018-12-15_15:07:47.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterKevin Leung
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList6x(13)C,4x(15)N labeled L-arginine; 6x(13)C,2x(15)N labeled L-lysine; deamidated L-asparagine; S-carboxamidomethyl-L-cysteine
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-10-07 18:02:23ID requested
12018-12-15 15:07:48announced
Publication List
no publication
Keyword List
submitter keyword: AML, Azacitidine, surface proteomics
Contact List
James Wells
contact affiliationUCSF
contact emailjim.wells@ucsf.edu
lab head
Kevin Leung
contact affiliationUCSF
contact emailkevin.leung@ucsf.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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