{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:36:58Z","timestamp":1791571018251,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2018\/30\/E\/NZ2\/00801"],"award-info":[{"award-number":["2018\/30\/E\/NZ2\/00801"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2018\/30\/E\/NZ2\/00801"],"award-info":[{"award-number":["2018\/30\/E\/NZ2\/00801"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004421","name":"Warsaw University of Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004421","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00y0xnp53","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Maria Sklodowska-Curie National Research Institute of Oncology"},{"id":[{"id":"https:\/\/ror.org\/02201aj62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute myeloid leukaemia (AML) is a therapeutically challenging malignancy driven by the self-renewal, quiescence, and therapy resistance of leukaemic stem cells (LSCs). CDK8, a kinase component of the Mediator complex, regulates oncogenic transcription, and the selective CDK8\/CDK19 inhibitor RVU120 (Romaciclib) targets AML cells with CD34+\/pSTAT5-high LSC-like characteristics; however, the epigenetic and transcriptional consequences of CDK8 blockade and actionable combinatorial strategies remain incompletely defined. Using the TEX cell line, an LSC-enriched surrogate model, we performed time-resolved RNA-seq, whole-proteome and phosphoproteomics mass spectrometry (MS), and CUT&amp;Tag chromatin profiling following treatment with RVU120 and CCT251921. CDK8 protein\u2013protein interactions were mapped by co-immunoprecipitation MS across five AML models, and synergy with Pelabresib (BET inhibitor) or CB6644 (RUVBL1\/2 inhibitor) was assessed by high-content screening in three cell lines and three patient-derived xenograft (PDX) models. Both inhibitors suppressed STAT5 phosphorylation, induced loss of the CD34+\/CD38\u2212 LSC-enriched phenotype, and drove erythromegakaryocytic differentiation. Transcriptomic and proteomic responses were concordant, and CDK8 inhibition triggered widespread enhancer activation with redistribution of RNAP2, BRD3, and NFRKB. CDK8 combined with Pelabresib acted synergistically in MOLM-16 cells and two of three PDX models. These findings identify CDK8 as a transcriptional node of LSC-associated programs and provide a mechanistic rationale for combined CDK8-BET inhibition in molecularly defined AML subsets, which will require validation in functional LSC assays and primary specimens.<\/jats:p>","DOI":"10.3390\/cells15151414","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:30:52Z","timestamp":1785861052000},"page":"1414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Multi-Omics and Interactome Analysis of CDK8 Inhibition Reveals Erythroid Differentiation Programs and Therapeutic Synergy with BET Blockade in AML"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-1909","authenticated-orcid":false,"given":"Malgorzata","family":"Statkiewicz","sequence":"first","affiliation":[{"name":"Laboratory of Cancer Metabolism, Department of Experimental 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Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kulecka","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Metabolism, Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"},{"name":"Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-7279","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Cendrowski","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Metabolism, Department of Experimental Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Cubulska-Lubak","sequence":"additional","affiliation":[{"name":"Laboratory of 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Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-7543","authenticated-orcid":false,"given":"Wioletta","family":"Slusarczyk-Kacprzyk","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-1008","authenticated-orcid":false,"given":"Krzysztof","family":"Goryca","sequence":"additional","affiliation":[{"name":"Genomics Core Facility, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-414X","authenticated-orcid":false,"given":"Tymon","family":"Rubel","sequence":"additional","affiliation":[{"name":"Institute of Radioelectronics and Multimedia Technology, Warsaw University of Technology, 00-661 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8542-2234","authenticated-orcid":false,"given":"Magdalena","family":"Bakun","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9373-4008","authenticated-orcid":false,"given":"Bianka","family":"Swiderska","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8927-5227","authenticated-orcid":false,"given":"Kamila","family":"Kruczkowska-Tarantowicz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hematology, Military Institute of 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Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103710","DOI":"10.1016\/j.critrevonc.2022.103710","article-title":"Leukemic Stem Cells as a Target for Eliminating Acute Myeloid Leukemia: Gaps in Translational Research","volume":"175","author":"Khaldoyanidi","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1158\/0008-5472.CAN-12-0255","article-title":"STAT5 Is Crucial to Maintain Leukemic Stem Cells in Acute Myelogenous Leukemias Induced by MOZ-TIF2","volume":"73","author":"Tam","year":"2013","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute Myeloid Leukemia","volume":"373","author":"Weisdorf","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/j.bbapap.2015.05.011","article-title":"CDK8 Kinase--An Emerging Target in Targeted Cancer Therapy","volume":"1854","author":"Rzymski","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33779","DOI":"10.18632\/oncotarget.16810","article-title":"SEL120-34A Is a Novel CDK8 Inhibitor Active in AML Cells with High Levels of Serine Phosphorylation of STAT1 and STAT5 Transactivation Domains","volume":"8","author":"Rzymski","year":"2017","journal-title":"Oncotarget"},{"key":"ref_7","first-page":"re3","article-title":"Revisiting Protein Kinase-Substrate Interactions: Toward Therapeutic Development","volume":"9","author":"Ferraz","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.celrep.2016.03.030","article-title":"Identification of Mediator Kinase Substrates in Human Cells Using Cortistatin A and Quantitative Phosphoproteomics","volume":"15","author":"Poss","year":"2016","journal-title":"Cell Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1093\/nar\/gkad538","article-title":"CDK8 and CDK19: Positive Regulators of Signal-Induced Transcription and Negative Regulators of Mediator Complex Proteins","volume":"51","author":"Chen","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/s41467-025-56335-6","article-title":"Temporal Phosphoproteomics Reveals Circuitry of Phased Propagation in Insulin Signaling","volume":"16","author":"Turewicz","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/s41580-022-00498-3","article-title":"The Mediator Complex as a Master Regulator of Transcription by RNA Polymerase II","volume":"23","author":"Richter","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1039\/D0RA07971E","article-title":"Bromodomain and BET Family Proteins as Epigenetic Targets in Cancer Therapy: Their Degradation, Present Drugs, and Possible PROTACs","volume":"11","author":"Muddassir","year":"2020","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.cell.2013.03.036","article-title":"Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers","volume":"153","author":"Hoke","year":"2013","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/s41416-021-01321-0","article-title":"Achieving Clinical Success with BET Inhibitors as Anti-Cancer Agents","volume":"124","author":"Shorstova","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nature14904","article-title":"Mediator Kinase Inhibition Further Activates Super-Enhancer-Associated Genes in AML","volume":"526","author":"Pelish","year":"2015","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pakulska, U., Obacz, M., Wo\u017anicki, J., Wiklik, K., Chakraborty, S., Micek, M., Mohanty, V., Coelho, D., Adamczyk, E., and Go\u0142as, A. (2026). Romaciclib, a CDK8\/CDK19 Inhibitor, Can Overcome Venetoclax Resistance through a Combinatorial Strategy. bioRxiv.","DOI":"10.64898\/2025.12.16.693978"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jiang, H., Lei, R., Ding, S.-W., and Zhu, S. (2014). Skewer: A Fast and Accurate Adapter Trimmer for next-Generation Sequencing Paired-End Reads. BMC Bioinform., 15.","DOI":"10.1186\/1471-2105-15-182"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python Framework to Work with High-Throughput Sequencing Data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1038\/sj.leu.2403917","article-title":"Direct Evidence for Cooperating Genetic Events in the Leukemic Transformation of Normal Human Hematopoietic Cells","volume":"19","author":"Warner","year":"2005","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1158\/0008-5472.CAN-09-0075","article-title":"ERG Is a Megakaryocytic Oncogene","volume":"69","author":"Smooha","year":"2009","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15437","DOI":"10.1073\/pnas.1213454109","article-title":"Hematopoietic Overexpression of the Transcription Factor Erg Induces Lymphoid and Erythro-Megakaryocytic Leukemia","volume":"109","author":"Carmichael","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/stem.2834","article-title":"Concise Review: Bipotent Megakaryocytic-Erythroid Progenitors: Concepts and Controversies","volume":"36","author":"Krause","year":"2018","journal-title":"Stem Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1021\/acs.jmedchem.5b01685","article-title":"Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19","volume":"59","author":"Mallinger","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1182\/blood-2016-01-693705","article-title":"Adult Human Megakaryocyte-Erythroid Progenitors Are in the CD34+CD38mid Fraction","volume":"128","author":"Sanada","year":"2016","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Katiyar, S., Shah, A., Rahman, K., Tripathy, N.K., Kashyap, R., Nityanand, S., and Chaturvedi, C.P. (2023). Analysis of Immunophenotypic Changes during Ex Vivo Human Erythropoiesis and Its Application in the Study of Normal and Defective Erythropoiesis. Cells, 12.","DOI":"10.3390\/cells12091303"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ward, C.M., and Ravid, K. (2020). Matrix Mechanosensation in the Erythroid and Megakaryocytic Lineages. Cells, 9.","DOI":"10.3390\/cells9040894"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11152","DOI":"10.1038\/s41467-025-64937-3","article-title":"Transcriptional Regulation of Protein Synthesis by Mediator Kinase Represents a Therapeutic Vulnerability in MYC-Driven Medulloblastoma","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/emboj.2010.3","article-title":"Crosstalk between C\/EBPbeta Phosphorylation, Arginine Methylation, and SWI\/SNF\/Mediator Implies an Indexing Transcription Factor Code","volume":"29","author":"Pless","year":"2010","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/embor.2010.75","article-title":"ATAC and Mediator Coactivators Form a Stable Complex and Regulate a Set of Non-Coding RNA Genes","volume":"11","author":"Krebs","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.molcel.2025.05.006","article-title":"Mediator Regulates Transcriptional Termination through Crosstalk with Pre-mRNA 3\u2032 End Processing Factors","volume":"85","author":"Lu","year":"2025","journal-title":"Mol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.molcel.2023.12.033","article-title":"Acetyl-CoA Production by Mediator-Bound 2-Ketoacid Dehydrogenases Boosts de Novo Histone Acetylation and Is Regulated by Nitric Oxide","volume":"84","author":"Russo","year":"2024","journal-title":"Mol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1021\/acschembio.8b00904","article-title":"CB-6644 Is a Selective Inhibitor of the RUVBL1\/2 Complex with Anticancer Activity","volume":"14","author":"Assimon","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s11899-023-00696-6","article-title":"Pelabresib (CPI-0610): An Exciting Novel Drug for the Treatment of Myelofibrosis","volume":"18","author":"Harrison","year":"2023","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Moore, J.E., Pratt, H.E., Fan, K., Phalke, N., Fisher, J., Elhajjajy, S.I., Andrews, G., Gao, M., Shedd, N., and Fu, Y. (2026). An Expanded Registry of Candidate Cis-Regulatory Elements. Nature.","DOI":"10.1038\/s41586-025-09909-9"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s12964-023-01206-0","article-title":"Enhancer RNAs: Mechanisms in Transcriptional Regulation and Functions in Diseases","volume":"21","author":"Li","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41594-022-00787-7","article-title":"Building Regulatory Landscapes Reveals That an Enhancer Can Recruit Cohesin to Create Contact Domains, Engage CTCF Sites and Activate Distant Genes","volume":"29","author":"Rinzema","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1182\/blood-2016-10-696054","article-title":"Biology and Relevance of Human Acute Myeloid Leukemia Stem Cells","volume":"129","author":"Thomas","year":"2017","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.18632\/oncotarget.28305","article-title":"MK256 Is a Novel CDK8 Inhibitor with Potent Antitumor Activity in AML through Downregulation of the STAT Pathway","volume":"13","author":"Lee","year":"2022","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1182\/blood.2021011044","article-title":"Molecular and Cellular Mechanisms That Regulate Human Erythropoiesis","volume":"139","author":"Caulier","year":"2022","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1172\/JCI61462","article-title":"Regulation of Lipogenesis by Cyclin-Dependent Kinase 8-Mediated Control of SREBP-1","volume":"122","author":"Zhao","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"dmm049650","DOI":"10.1242\/dmm.049650","article-title":"Cdk8 Attenuates Lipogenesis by Inhibiting SREBP-Dependent Transcription in Drosophila","volume":"15","author":"Li","year":"2022","journal-title":"Dis. Models Mech."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e20201545","DOI":"10.1084\/jem.20201545","article-title":"Inflammatory Signaling Regulates Hematopoietic Stem and Progenitor Cell Development and Homeostasis","volume":"218","author":"Collins","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exphem.2023.05.001","article-title":"Dynamics of Human Hematopoietic Stem and Progenitor Cell Differentiation to the Erythroid Lineage","volume":"123","author":"Schippel","year":"2023","journal-title":"Exp. Hematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1423-0410.2010.01453.x","article-title":"The Influence of Extracellular Matrix Proteins and Mesenchymal Stem Cells on Erythropoietic Cell Maturation","volume":"101","author":"Dorn","year":"2011","journal-title":"Vox Sang."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41375-019-0532-7","article-title":"A Three-Dimensional in Vitro Model of Erythropoiesis Recapitulates Erythroid Failure in Myelodysplastic Syndromes","volume":"34","author":"Dimitriou","year":"2020","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s10020-024-00849-0","article-title":"Downregulation of HNRNPA1 Induced Neoantigen Generation via Regulating Alternative Splicing","volume":"30","author":"Sun","year":"2024","journal-title":"Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1042\/BCJ20220075","article-title":"NUCKS1 Is a Highly Modified, Chromatin-Associated Protein Involved in a Diverse Set of Biological and Pathophysiological Processes","volume":"479","author":"Grundt","year":"2022","journal-title":"Biochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E159","DOI":"10.1073\/pnas.1102140108","article-title":"Bromodomain Protein Brd3 Associates with Acetylated GATA1 to Promote Its Chromatin Occupancy at Erythroid Target Genes","volume":"108","author":"Lamonica","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/s41594-022-00840-5","article-title":"Distinct Roles for CKM-Mediator in Controlling Polycomb-Dependent Chromosomal Interactions and Priming Genes for Induction","volume":"29","author":"Dimitrova","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1158\/2159-8290.CD-21-0956","article-title":"Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts","volume":"12","author":"Ellegast","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"D512","DOI":"10.1093\/nar\/gku1267","article-title":"PhosphoSitePlus, 2014: Mutations, PTMs and Recalibrations","volume":"43","author":"Hornbeck","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10503","DOI":"10.1038\/s41598-019-46385-4","article-title":"Large-Scale Discovery of Substrates of the Human Kinome","volume":"9","author":"Sugiyama","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D542","DOI":"10.1093\/nar\/gkx1104","article-title":"iPTMnet: An Integrated Resource for Protein Post-Translational Modification Network Discovery","volume":"46","author":"Huang","year":"2018","journal-title":"Nucleic Acids Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:24:54Z","timestamp":1785990294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":54,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15151414"],"URL":"https:\/\/doi.org\/10.3390\/cells15151414","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}