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Corveleyn"],"software":[""],"tissue":["T Cell"],"sample_protocol":["Patient-derived  T-ALL cells from PDX mouse models were quickly thawn in aMEM medium (Gibco, Waltham, MA, USA) supplemented with 10% heat-inactivated fetal calf serum after which cell pellets of 5 million cells were collected and snap-frozen in liquid nitrogen. Histone extraction of the cells was performed using direct acid extraction as described previously. Consequently, one-dimensional SDS-PAGE on a 9-18% TGX gel (Bio-Rad Laboratories, Hercules, CA, USA) was performed on a fraction of the resulting extracts for histone quantification and normalization. The remaining histone extracts were propionylated and digested following an established protocol.The propionylated and digested samples were resuspended in 0.1% formic acid and injection volumes were adjusted resulting in 800 ng of histones on column. A quality control mixture was created by mixing 2 μl of each sample. Data-dependent acquisition (DDA) was performed on a ZenoTOF 7600 system (AB Sciex, Marlborough, MA, USA) operating in positive mode coupled to an ACQUITY UPLC M-Class System (Waters Corporation, Milford, MA, USA) operating in capillary flow mode (5 μl min−1). Trapping and separation of the peptides was carried out on a Triart C18 column (5 mm × 0.5 mm; YMC Europe GmbH, Dinslaken, Germany) and a Luna Omega Polar C18 column at 45°C (150 mm × 0.3 mm; particle size 3 µm; Phenomenex, Torrance, CA, USA), respectively, using a low pH reverse-phase gradient. Buffers A and B of the mobile phase consisted of 0.1% formic acid in water and in acetonitrile (Biosolve Chimie, Dieuze, France), respectively. A 20-min non-linear gradient going from 2% to 50% Buffer B, followed by a washing step at 90% mobile phase B and an equilibration step at 2% mobile phase B (starting conditions). The samples were run in a randomized fashion and a quality control injection was incorporated every ten samples. For each cycle, one full MS1 scan (m/z 350–1,250) of 100 ms was followed by an MS2 (m/z 140–1,800, high-sensitivity mode) of 12 ms. A maximum of 40 precursors (charge state +2 to +6) exceeding 1500 c.p.s. were monitored, followed by an exclusion for 3 s per cycle. A collision energy of 12 V and a cycle time of 800 ms was applied. Ion source parameters were set to 4.5 kV for the ion spray voltage, 35 psi for the curtain gas, 15 psi for nebulizer gas (ion source gas 1), 60 psi for heater gas (ion source gas 2) and 200 °C as source temperature."],"repository":["Pride"],"labhead":["Maarten Dhaenens"],"instrument_platform":[""],"labhead_affiliation":["ProGenTomics Laboratory of Pharmaceutical Biotechnology, Ghent University, Belgium"],"submission_type":["COMPLETE"],"publication":["41882219 Corveleyn L, Provez L, Satilmis O, Refhagen N, Landfors M, Sleeckx W, Lintermans B, De Maesschalck A, Kotecha RS, De Moerloose B, Lammens T, Deforce D, Degerman S, Goossens S, Van Vlierberghe P, Dhaenens M. Profiling histone post-translational modifications to identify signatures of epigenetic drug response in T-cell acute lymphoblastic leukemia. Sci Rep. 2026 16(1):15029 10.1038/s41598-026-44665-4"],"submitter_affiliation":["ProGenTomics, Ghent University"],"labhead_mail":["maarten.dhaenens@ugent.be"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics"],"disease":["Acute T Cell Leukemia"],"submitter_keywords":["Histone post-translational modifications","Lc-ms","Epigenetics","Pharmacoepigenetics","T-all"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD067935"],"quantification_method":[""],"modification":[""],"data_protocol":["Raw data from all runs were imported and all runs were aligned in a single experiment in Progenesis QIP 4.2 (Nonlinear Dynamics - Waters, Newcastle upon Tyne, UK) for feature detection. Next, the 20 MS/MS spectra closest to the elution apex were selected for each precursor ion and merged into a single ∗.mgf file to search in Mascot (Matrix Science Ltd, London, UK). Mascot is a database search engine that uses a probabilistic scoring algorithm to define peptide-to-spectrum matches (PSM). Two types of searches were performed on this file: 1) a quality search to verify the presence of non-propionylated standards (ß-gal), and to assess the extent of underpropionylation; and 2) an error tolerant search to identify the proteins present in the sample, and to determine the best set of 9 hPTMs for further analysis. The Mascot search parameters used for both searches are shown in Table 2. A new FASTA-database was generated based on the results from the error tolerant search for further analysis. Next, the three MS/MS spectra closest to the elution apex were merged into a single *.mgf and exported to perform a biological search in Mascot (Table 2). The search results (∗.xml-format) were imported back into Progenesis QIP 4.2 to annotate the features from which they originated. Features that were annotated as histone peptidoforms were manually validated by an expert to resolve isobaric near-coelution (Figure 2). Consequently, runs were normalized against all histone peptides in order to assure a constant histone protein abundance, since we aim to quantify changes in hPTMs and not in the expression of histones themselves. Outliers were removed based on normalization factor (greater than 10 and less than 0,3) and PCA clustering of all histone peptidoforms. Finally, deconvoluted peptide ion data (*.csv format) from all histones were exported from Progenesis QIP 4.2 for PTM summarization using msqrob2PTM."],"omics_type":["Proteomics"],"species":["Homo Sapiens (human)"],"submitter_mail":["lcorvele@gmail.com"],"submitter_country":["Belgium"],"doi":["10.6019/PXD067935"],"pubmed_title":["Profiling histone post-translational modifications to identify signatures of epigenetic drug response in T-cell acute lymphoblastic leukemia."],"pubmed_authors":["Corveleyn Laura L, Provez Lien L, Satilmis Osman O, Refhagen Nina N, Landfors Mattias M, Sleeckx Wouter W, Lintermans Beatrice B, De Maesschalck Amélie A, Kotecha Rishi S RS, De Moerloose Barbara B, Lammens Tim T, Deforce Dieter D, Degerman Sofie S, Goossens Steven S, Van Vlierberghe Pieter P, Dhaenens Maarten M"],"additional_accession":[]},"is_claimable":false,"name":"Profiling histone post-translational modifications to identify signatures of epigenetic drug response in T-cell acute lymphoblastic leukemia","description":"Epigenetic modifications are dynamic and reversible, making them attractive targets for therapeutic intervention in cancer. Although several epigenetic drugs (epidrugs) have been clinically approved, their application in T-cell acute lymphoblastic leukemia (T-ALL) remains limited, and predictive biomarkers of response are lacking. Here, we present a mass spectrometry (MS)-based pharmacoepigenetic approach to profile histone post-translational modifications (hPTMs) to identify signatures associated with epidrug sensitivity in T-ALL. Baseline hPTM landscapes were previously established by our group for 21 T-ALL cell lines using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Here, we treated these cell lines with a panel of nine epidrugs including anthracyclines, histone deacetylase inhibitors, and DNA methyltransferase inhibitors. Correlation of cell viability data with hPTM levels revealed distinct hPTM signatures linked to sensitivity for each drug class. These signatures were subsequently evaluated in T-ALL patient-derived xenograft (PDX) models. However, we our analysis revealed substantial discepancies in hPTM sensitivity signatures compared to those observed in vitro. Co-variation network analysis highlighted divergence in hPTM-hPTM correlation between the two models, underscoring limitations of cell lines for modeling dynamic epigenetic regulation in vivo. Our findings establish a framework for MS-based hPTM profiling in T-ALL and emphasize the importance of model selection in developing predictive epigenetic biomarkers.","dates":{"publication":"2026-06-08","submission":"2025-09-01"},"accession":"PXD067935","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:1129","NEWT:309807","NEWT:55153","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:43186","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:638632","NEWT:263737","NEWT:224326","NEWT:1333499","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:96731","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:192875","NEWT:1214915","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:658457","NEWT:1310161","NEWT:77133","NEWT:295358","NEWT:145481","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:633149","NEWT:10239","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1235816","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:2065263","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:52283","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:3702","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:33548","NEWT:274","NEWT:7070","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:9483","NEWT:333760","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:84588","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:1502","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NCBITaxon:4932","NEWT:109760","NEWT:943274","NEWT:644223","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:352472","NEWT:1071661","NEWT:1202532","NEWT:360094","NEWT:470","NEWT:41364","NEWT:1313","NEWT:1218097","NEWT:39491","NCBITaxon:5811","NEWT:29491","NEWT:2014887","NEWT:33952","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:215402","NCBITaxon:548681","NEWT:272634","NEWT:9031","NEWT:1872122","NEWT:7091","NEWT:1034015","NEWT:141262","NEWT:108931","NEWT:1055524","NEWT:4087","NEWT:9778","NEWT:306","NEWT:150475","NEWT:303","NEWT:267872","NEWT:7111","NEWT:347515","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:4090","NEWT:4092","NEWT:9541","NEWT:8694","NEWT:4093","NEWT:4096","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:941442","NEWT:536088","NEWT:13076","NEWT:1226408","NEWT:7108","NEWT:40479","NEWT:43989","NEWT:4076","NEWT:142615","NEWT:317","NEWT:1006581","NEWT:885318","NEWT:39488","NEWT:550","NEWT:4081","NEWT:273068","NEWT:554","NEWT:98334","NEWT:451516","NEWT:4084","NEWT:63577","NEWT:36185","NEWT:1225786","NEWT:7574","NEWT:1715256","NEWT:30640","NEWT:575412","NEWT:929793","NEWT:29204","NEWT:28112","NEWT:114155","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:6239","NEWT:162425","NEWT:216257","NEWT:102169","NEWT:9986","NEWT:4054","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8655","NEWT:98351","NEWT:1263854","NEWT:118503","NEWT:2059687","NEWT:160488","NEWT:28104","NEWT:207559","NEWT:407821","NCBITaxon:2","NEWT:85057","NEWT:985076","NEWT:568708","NEWT:1215323","NEWT:986","NEWT:52641","NEWT:7159","NEWT:267671","NEWT:28532","NEWT:353152","NEWT:8496","NEWT:7165","NEWT:27448","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:24323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