Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LC-MSMS of the MHC-I immunopeptidome of AML cell lines

ABSTRACT: The hypomethylating agent 5-azacytidine (AZA) is the first-line induction therapy for AML patients unsuitable for intensive chemotherapy. The anti-tumor effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, clear evidence supporting higher ERE MAPs presentation after AZA treatment in AML is lacking. Therefore, we examined the immunopeptidome of four AML cell lines treated with AZA through a proteogenomic approach to validate this hypothesis.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell

DISEASE(S): Acute Myeloid Leukemia

SUBMITTER: Courcelles Mathieu

LAB HEAD: Pierre Thibault

PROVIDER: PXD038663 | Pride | 2024-04-17

REPOSITORIES: pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	MOLM-13_Aza_TMT_110321_rep1.mgf	Mgf
	MOLM-13_Aza_TMT_110321_rep1.raw	Raw
	MOLM-13_Aza_TMT_110321_rep2.mgf	Mgf
	MOLM-13_Aza_TMT_110321_rep2.raw	Raw
	MOLM-13_Aza_TMT_110321_rep3.mgf	Mgf

Items per page:

1 - 5 of 70

Similar Datasets

LC-MSMS of the MHC-I immunopeptidome of AML cell line, THP-1

Project description:The hypomethylating agent 5-azacytidine (AZA) is the first-line induction therapy for AML patients unsuitable for intensive chemotherapy. The anti-tumor effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, clear evidence supporting higher ERE MAPs presentation after AZA treatment in AML is lacking. Interestingly, we find that AZA-mediated DNMT2 inhibition leads to autophagy induction, which is responsible for mitigating ERE MAPs generation. To validate our findings, we examined the immunopeptidome of THP-1 cells treated with AZA combined with autophagy inhibitor, Spautin-1 or decitabine (DAC, non-DNMT2 inhibiting HMA) through a proteogenomic approach.

2024-04-17 | PXD046853 | Pride

LC-MSMS of the MHC-I immunopeptidome of human iPSCs

Project description:The development of cancer immunotherapeutics is limited by the discovery of actionable tumor-specific antigens (TSAs), which need to be presented at high levels on cancer cells, but not presented by normal tissues or presented at levels below the threshold for T-cell recognition to prevent autoimmunity. Accumulating evidence indicates that pluripotent stem cells (PSCs), namely embryonic stem cells (ESCs) and induced PSCs (iPSCs), express a class of pluripotency-associated MHC-I-associated peptides (paMAPs) that can be recognized by tumor-specific T cells. Hence, being strictly confined to the embryonic stage of development and absent from healthy adult tissues, paMAPs shared by iPSCs and tumors would represent ideal targets for the development of TSA-based vaccines against a wide range of cancers. We performed immunopeptidomic analyses of human iPSCs and we identified a set of paMAPs that could serve for the design of TSA-based vaccines against many cancers.

2022-08-22 | PXD026702 | Pride

LC-MSMS of OVCAR-3 class I immunopeptidome

Project description:Endogenous retroelements (ERE) constitute about 42% of the human genome and have been implicated in common human diseases such as autoimmunity and cancer. Despite evidence that some EREs can be expressed at the RNA and protein levels in specific contexts, a systems-level evaluation of their expression in human tissues is lacking. We report that all human tissues express EREs but the breadth and magnitude of ERE expression are very heterogeneous from one tissue to another. ERE expression was particularly high in two MHC-I-deficient tissues (ESCs and testis) and one MHC-I-expressing tissue, mTECs. In mutant mice, we report that the exceptional expression of EREs in mTECs was AIRE-independent. MS analyses identified 103 non-redundant ERE-derived MAPs (ereMAPs) in B-LCLs. These ereMAPs preferentially derived from sense translation of intronic EREs. Notably, detailed analyses of their amino acid composition revealed that ERE-derived MAPs presented homology to viral MAPs. This study shows that ERE expression in somatic tissues is more pervasive and heterogeneous than anticipated. The high and diversified expression of EREs in mTECs and their ability to generate MAPs suggest that EREs may play an important role in the establishment of self-tolerance. The viral-like properties of ERE-derived MAPs suggest that those not expressed in mTECs can be highly immunogenic.

2020-05-26 | PXD018124 | Pride

Expression data from AML cell lines

Project description:Post-chemotherapy relapse presents a major unmet medical need in AML where treatment options are limited. We used gene expression profile from 32 AML cell lines to characterize expression difference between responder and non-responders to PIM inhibitors. Our results highlight the importance of STAT5 and MYC in rendering cancer cells sensitive to PIM inhibitors. All AML cell lines were purchased from either ATCC or DSMZ and cultured accordingly to vendorsM-bM-^@M-^Y protocols. Gene expression were measured from the cell lines using Affymetrix microarrays. Response to PIM inhibitors (IC50) was recorded for each cell line, and association between drug response and gene expression were analyzed.

2014-07-29 | E-GEOD-59808 | biostudies-arrayexpress

RNA-seq of SUPT1, LOUCY, JURKAT and DND41 after treatment with 5-azacytidine and Vitamin C

Project description:TET2 is a know tumorsuppressor gene involved in the demethylation of DNA. TET2 catalyses the conversion of 5-methyl cytosine (5-mC) to 5-hydroximethyl cytosine (5-hmC), an important step in the removal of methylation from the DNA. In T-All mutations in TET2 are rare, however we have found that it is often silenced by DNA Methylation. 5-Azacytidine (5-AZA) is a an effective demethylating agent used as a cancer treatment and has been showed to be able to reactivate methylated genes. Similarly, Vitamin C is an important co-factor for TET2 and has been shown to have synergistic effects with 5-Azacytidine. By treating the TET2 methylated T-ALL cell lines Loucy and DND41 and comparing to TET2 expressing T-ALL cells lines such as SUP-T1 and Jurkat we aimed to explore if 5-AZA could reactivate TET2 in T-ALL, what effects this would have on tumorgenicity and whether Vitamin C had any synergy with these effects in T-ALL. As part of this effort we treated the cell lines SUP-T1, Jurkat, Loucy and DND41 with 5-AZA and Vitamin C and performed Total RNA-seq to explore the effects of 5-AZA and Vitamin C on the expression of genes and non-coding elements such as retrotransponsons.

2021-08-04 | E-MTAB-10512 | biostudies-arrayexpress

Multi-omics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell surface proteome

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

Promiscuous targeting of bromodomains by Bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-10-25 | E-GEOD-78830 | biostudies-arrayexpress

The phosphoproteomic landscape of 16 Acute Myeloid Leukemia (AML) cell lines

Project description:Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in AML cell lines as targets and predictive biomarkers to select KIs for treatment. We identified 3605 class I phosphorylation sites in 16 AML cell lines (EOL-1, KG-1a, MM6, KG-1, ME-1, NB-4, Kasumi-3, MV4-11, THP-1, HEL, HL-60, Kasumi-1, Kasumi-6, ML-2, OCI-AML3, MOLM-13) that exhibited large variation in the number and level of phosphopeptides per cell line (241-2764). Ranking analyses successfully pinpointed the hyperactive kinases PDGFRA, FGFR1, KIT, and FLT3 in eight cell lines with a corresponding kinase mutation. Additionally, we identified unexpected drivers in two more cell lines (PDGFRA in Kasumi-3 and FLT3 in MM6) which proved sensitive to specific kinase inhibitors. Six cell lines without a clear receptor tyrosine kinase (RTK) driver showed evidence of MAPK1/3 activation, consistent with the presence of activating RAS mutations. Our data show the potential of pY phosphoproteomics to identify key drivers in AML cells, and the predictive value of the phosphoproteome profiles in TKi selection for targeted treatment.

2019-11-11 | PXD007237 | Pride

Promiscuous targeting of bromodomains by Bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia [set 1]

Project description:Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET inhibitors and their significant activity in diverse tumor models has rapidly translated into clinical studies and has motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of bromodomain protein complexes complicates predictions of consequences of their pharmacological targeting. To address this issue we developed a promiscuous bromodomain inhibitor (bromosporine, BSP) that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle we studied the effect of BSP in leukemic cell-lines known to be sensitive to BET inhibition and found as expected strong anti-proliferative activity. Comparison of the modulation of transcriptional profiles by BSP at short inhibitor exposure resulted in a BET inhibitor signature but no significant additional changes in transcription that could account for inhibition of other BRDs. Thus, non-selective targeting of BRDs identified BETs, but not other BRDs, as master regulators of a context dependent primary transcription response. Cells were seeded the day prior to treatment at 2x10^5 per ml. Treatments were performed so that a final concentration of 0.1 % DMSO (Cat.#D1435; Sigma) was achieved and cells were incubated with DMSO or 500 nM test compound (BSP or JQ1) for 6 h prior to isolation of RNA. Total RNA was isolated using a standard TRIzol (Invitrogen) protocol and prepared using RNeasy columns (Cat.#74106 plus; Qiagen). RNA was quantified using a Nanodrop spectrophotometer (model ND1000; Thermo Fisher) and integrity assessed on a BioAnalyzer (2100; Agilent Laboratories, USA). All samples had a RNA Integrity Number (RIN) â?¥ 9. Biological triplicates were performed for each condition tested.

2016-10-25 | E-GEOD-78827 | biostudies-arrayexpress

Extending the Comprehensiveness of Immunopeptidome Analyses Using Isobaric Peptide Labeling

Project description:Defining the repertoire of peptides presented by the major histocompatibility complex class I (MHC I) is a key step towards the identification of relevant antigens for cancer immunotherapy. However, the identification of the cancer-specific antigens is a significant analytical challenge in view of their low abundance and low mutational load found in primary cancer specimens. Here, we describe the application of isobaric peptide labeling with tandem mass tag (TMT) to improve the detection of the MHC I peptides. Isobaric peptide labeling was found to promote the formation of multiply-charged ions and to enhance the formation of b-type fragment ions, thus resulting in a 50% improvement of MHC I peptide identification. The gain in sensitivity obtained using TMT labeling enabled the detection of low abundance MHC I peptides including tumor-specific antigens (TSAs) and minor histocompatibility antigens (MiHAs). We further demonstrate the application of this approach to quantify MiHAs presented by B-cell lymphocytes and determined their expression levels by LC-MS/MS using both synchronous precursor selection (SPS) and high field asymmetric waveform ion mobility spectrometry (FAIMS).

2020-11-16 | PXD017918 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data