{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:21:47Z","timestamp":1764404507499,"version":"3.46.0"},"reference-count":70,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306882\/2023\u20100","405918\/2022\u20104"],"award-info":[{"award-number":["306882\/2023\u20100","405918\/2022\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/21801\u20102"],"award-info":[{"award-number":["2017\/21801\u20102"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acute myeloid leukaemia (AML) with isolated trisomies (ITs) represents a distinct cytogenetic subgroup with heterogeneous clinical behaviour and incompletely defined molecular features. To explore its genomic and transcriptomic landscape, we performed next\u2010generation sequencing (NGS) on 14 AML patients harbouring isolated trisomies of chromosomes 8, 9, 10, 13, 14, 21 and 22. RNA sequencing (RNA\u2010Seq) was conducted on 15 samples, including 12 with IT and 3 cytogenetically normal AML cases (normal karyotype, NK\u2010AML) serving as controls. Trisomy 8 was most frequent, followed by chromosomes 13, 14 and 21. Recurrent mutations were identified in epigenetic regulators (\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    ,\n                    <jats:italic>IDH1\/2<\/jats:italic>\n                    ,\n                    <jats:italic>ASXL1<\/jats:italic>\n                    ,\n                    <jats:italic>TET2<\/jats:italic>\n                    ). Transcriptomic profiling stratified cases into IT\u20108, IT\u201021 and IT\u201013+22 subgroups. Gene set enrichment analysis (GSEA) revealed shared downregulation of cell cycle\u2010related pathways (e.g., G2M checkpoint) and subgroup\u2010specific patterns: oxidative stress and unfolded protein response in IT\u20108; epithelial\u2010mesenchymal transition and oxidative phosphorylation in IT\u201021; inflammatory signalling (IL\u20106\/JAK\/STAT, TNF\u2010\u03b1\/NF\u2010\u03baB) in IT\u201013+22. A core set of 60 differentially expressed genes (DEGs) was shared, with nine hub genes related to cell cycle (\n                    <jats:italic>MCM4<\/jats:italic>\n                    ,\n                    <jats:italic>CDC7<\/jats:italic>\n                    ,\n                    <jats:italic>CDC25A<\/jats:italic>\n                    ,\n                    <jats:italic>DHFR<\/jats:italic>\n                    ), proteostasis (\n                    <jats:italic>HSPA5<\/jats:italic>\n                    ,\n                    <jats:italic>DNAJC3<\/jats:italic>\n                    ,\n                    <jats:italic>CALR<\/jats:italic>\n                    ,\n                    <jats:italic>HSP90B1<\/jats:italic>\n                    ) and inflammation. Drug sensitivity profiling revealed subgroup\u2010specific vulnerabilities: IT\u20108 to DNA damage checkpoint inhibitors, IT\u201021 to PLK\/mTOR inhibitors and IT\u201013+22 to BRAF\/EGFR\u2010targeted agents. These findings highlight AML\u2010IT heterogeneity and therapeutic potential.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70941","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T04:35:41Z","timestamp":1764304541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Genomic and Transcriptomic Profiling of Isolated Trisomies in\n                    <scp>AML<\/scp>\n                    Reveals Cell Cycle Dysregulation and Therapeutic Vulnerabilities"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-3158","authenticated-orcid":false,"given":"Jersey Heitor da S.","family":"Mau\u00e9s","sequence":"first","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6155-3253","authenticated-orcid":false,"given":"Bruno Kosa L.","family":"Duarte","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-5335","authenticated-orcid":false,"given":"Maria Carolina C. M.","family":"Svidnicki","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2226-4311","authenticated-orcid":false,"given":"Herton Luiz A. S.","family":"Filho","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6034-1366","authenticated-orcid":false,"given":"Fernanda Soares","family":"Niemann","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana da Silva S.","family":"Duarte","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-7203","authenticated-orcid":false,"given":"Paula","family":"de Melo Campos","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-786X","authenticated-orcid":false,"given":"Pedro M.","family":"Moraes\u2010Vieira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology\u2013Institute of Biology University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0809-8068","authenticated-orcid":false,"given":"Sara Teresinha","family":"Olalla Saad","sequence":"additional","affiliation":[{"name":"National Institute of Science and Technology of Blood (INCT) and Hematology and Transfusion Medicine Center (Hemocentro) University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_12_2_1","DOI":"10.1038\/s41375-019-0560-3"},{"doi-asserted-by":"publisher","key":"e_1_2_12_3_1","DOI":"10.1111\/ejh.12861"},{"doi-asserted-by":"publisher","key":"e_1_2_12_4_1","DOI":"10.1073\/pnas.98.3.1124"},{"doi-asserted-by":"publisher","key":"e_1_2_12_5_1","DOI":"10.1038\/s41467-022-32103-8"},{"doi-asserted-by":"publisher","key":"e_1_2_12_6_1","DOI":"10.1080\/17474086.2019.1657400"},{"doi-asserted-by":"publisher","key":"e_1_2_12_7_1","DOI":"10.1080\/16078454.2022.2071799"},{"doi-asserted-by":"publisher","key":"e_1_2_12_8_1","DOI":"10.1186\/1471-2407-10-401"},{"doi-asserted-by":"publisher","key":"e_1_2_12_9_1","DOI":"10.1007\/s12288-010-0035-1"},{"doi-asserted-by":"publisher","key":"e_1_2_12_10_1","DOI":"10.1182\/blood-2013-12-540716"},{"doi-asserted-by":"publisher","key":"e_1_2_12_11_1","DOI":"10.1155\/2010\/365318"},{"doi-asserted-by":"publisher","key":"e_1_2_12_12_1","DOI":"10.1016\/j.clml.2013.05.020"},{"doi-asserted-by":"publisher","key":"e_1_2_12_13_1","DOI":"10.1182\/blood-2016-08-733196"},{"doi-asserted-by":"publisher","key":"e_1_2_12_14_1","DOI":"10.3324\/haematol.2020.269134"},{"doi-asserted-by":"publisher","key":"e_1_2_12_15_1","DOI":"10.1200\/JCO.1990.8.5.813"},{"doi-asserted-by":"publisher","key":"e_1_2_12_16_1","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_12_17_1","first-page":"8","article-title":"CancerVar: An Artificial Intelligence\u2013Empowered Platform for Clinical Interpretation of Somatic Mutations in Cancer","volume":"8","author":"Li Q.","year":"2022","journal-title":"Science Advances"},{"doi-asserted-by":"publisher","key":"e_1_2_12_18_1","DOI":"10.1038\/gim.2015.30"},{"doi-asserted-by":"publisher","key":"e_1_2_12_19_1","DOI":"10.1101\/gr.239244.118"},{"doi-asserted-by":"publisher","key":"e_1_2_12_20_1","DOI":"10.1093\/bioinformatics\/bts635"},{"doi-asserted-by":"publisher","key":"e_1_2_12_21_1","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_2_12_22_1","article-title":"Three Differential Expression Analysis Methods for RNA Sequencing: Limma, EdgeR, DESeq2","volume":"2021","author":"Liu S.","year":"2021","journal-title":"Journal of Visualized Experiments"},{"doi-asserted-by":"publisher","key":"e_1_2_12_23_1","DOI":"10.1093\/bioinformatics\/btw313"},{"doi-asserted-by":"publisher","key":"e_1_2_12_24_1","DOI":"10.1093\/bioinformatics\/btab806"},{"doi-asserted-by":"publisher","key":"e_1_2_12_25_1","DOI":"10.1073\/pnas.0506580102"},{"unstructured":"G.Korotkevich V.Sukhov N.Budin et\u00a0al. \u201cFast Gene Set Enrichment Analysis \u201dBioRxiv (2021): 060012.","key":"e_1_2_12_26_1"},{"doi-asserted-by":"publisher","key":"e_1_2_12_27_1","DOI":"10.1089\/omi.2011.0118"},{"doi-asserted-by":"publisher","key":"e_1_2_12_28_1","DOI":"10.1093\/bib\/bbab260"},{"doi-asserted-by":"publisher","key":"e_1_2_12_29_1","DOI":"10.1056\/NEJMoa1516192"},{"doi-asserted-by":"publisher","key":"e_1_2_12_30_1","DOI":"10.1182\/bloodadvances.2021004556"},{"doi-asserted-by":"publisher","key":"e_1_2_12_31_1","DOI":"10.1182\/blood.2023023723"},{"issue":"25","key":"e_1_2_12_32_1","first-page":"00028","article-title":"Epigenetic Dysregulation in Acute Myeloid Leukemia","volume":"0037","author":"Schrezenmeier J.","year":"2025","journal-title":"Seminars in Hematology"},{"doi-asserted-by":"publisher","key":"e_1_2_12_33_1","DOI":"10.1080\/10428194.2018.1433298"},{"doi-asserted-by":"publisher","key":"e_1_2_12_34_1","DOI":"10.3390\/cancers13112655"},{"doi-asserted-by":"publisher","key":"e_1_2_12_35_1","DOI":"10.1038\/s41392-020-00235-2"},{"doi-asserted-by":"publisher","key":"e_1_2_12_36_1","DOI":"10.1016\/j.cub.2014.03.034"},{"doi-asserted-by":"publisher","key":"e_1_2_12_37_1","DOI":"10.1002\/bies.202200026"},{"doi-asserted-by":"publisher","key":"e_1_2_12_38_1","DOI":"10.1038\/ncb3184"},{"doi-asserted-by":"publisher","key":"e_1_2_12_39_1","DOI":"10.1182\/blood-2014-08-551499"},{"doi-asserted-by":"publisher","key":"e_1_2_12_40_1","DOI":"10.1038\/s41392-023-01342-6"},{"doi-asserted-by":"publisher","key":"e_1_2_12_41_1","DOI":"10.1111\/ijlh.13759"},{"doi-asserted-by":"publisher","key":"e_1_2_12_42_1","DOI":"10.1016\/j.bbcan.2021.188661"},{"doi-asserted-by":"publisher","key":"e_1_2_12_43_1","DOI":"10.1134\/S1990519X09060017"},{"doi-asserted-by":"publisher","key":"e_1_2_12_44_1","DOI":"10.1158\/2643-3230.BCD-23-0210"},{"doi-asserted-by":"publisher","key":"e_1_2_12_45_1","DOI":"10.1186\/s13059-014-0550-8"},{"doi-asserted-by":"publisher","key":"e_1_2_12_46_1","DOI":"10.1093\/bioinformatics\/btp616"},{"doi-asserted-by":"publisher","key":"e_1_2_12_47_1","DOI":"10.1186\/gb-2014-15-2-r29"},{"doi-asserted-by":"publisher","key":"e_1_2_12_48_1","DOI":"10.1002\/gcc.22880"},{"doi-asserted-by":"publisher","key":"e_1_2_12_49_1","DOI":"10.1016\/j.molcel.2004.07.012"},{"doi-asserted-by":"publisher","key":"e_1_2_12_50_1","DOI":"10.1186\/s12915-020-00852-x"},{"doi-asserted-by":"publisher","key":"e_1_2_12_51_1","DOI":"10.1186\/gb-2010-11-8-216"},{"doi-asserted-by":"publisher","key":"e_1_2_12_52_1","DOI":"10.1182\/blood.V104.11.2034.2034"},{"doi-asserted-by":"publisher","key":"e_1_2_12_53_1","DOI":"10.3324\/haematol.2022.280800"},{"doi-asserted-by":"publisher","key":"e_1_2_12_54_1","DOI":"10.3390\/cells14040269"},{"doi-asserted-by":"publisher","key":"e_1_2_12_55_1","DOI":"10.1158\/0008-5472.CAN-16-2074"},{"doi-asserted-by":"publisher","key":"e_1_2_12_56_1","DOI":"10.1038\/nrclinonc.2018.8"},{"doi-asserted-by":"publisher","key":"e_1_2_12_57_1","DOI":"10.1016\/S1044-579X(02)00133-5"},{"doi-asserted-by":"publisher","key":"e_1_2_12_58_1","DOI":"10.1186\/s13008-015-0009-7"},{"doi-asserted-by":"publisher","key":"e_1_2_12_59_1","DOI":"10.1016\/j.semcdb.2021.03.008"},{"doi-asserted-by":"publisher","key":"e_1_2_12_60_1","DOI":"10.3390\/cancers11010066"},{"doi-asserted-by":"publisher","key":"e_1_2_12_61_1","DOI":"10.1038\/oncsis.2017.72"},{"doi-asserted-by":"publisher","key":"e_1_2_12_62_1","DOI":"10.1038\/s41467-023-39332-5"},{"doi-asserted-by":"publisher","key":"e_1_2_12_63_1","DOI":"10.3324\/haematol.2013.093187"},{"doi-asserted-by":"publisher","key":"e_1_2_12_64_1","DOI":"10.1158\/0008-5472.CAN-08-1901"},{"doi-asserted-by":"publisher","key":"e_1_2_12_65_1","DOI":"10.1182\/blood.V122.21.4175.4175"},{"doi-asserted-by":"publisher","key":"e_1_2_12_66_1","DOI":"10.1186\/s13045-017-0443-x"},{"doi-asserted-by":"publisher","key":"e_1_2_12_67_1","DOI":"10.18632\/oncotarget.22178"},{"doi-asserted-by":"publisher","key":"e_1_2_12_68_1","DOI":"10.1111\/bjh.12518"},{"doi-asserted-by":"publisher","key":"e_1_2_12_69_1","DOI":"10.3389\/fonc.2021.801779"},{"doi-asserted-by":"publisher","key":"e_1_2_12_70_1","DOI":"10.18632\/oncotarget.6122"},{"doi-asserted-by":"publisher","key":"e_1_2_12_71_1","DOI":"10.1182\/blood.V120.21.3739.3739"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:18:00Z","timestamp":1764404280000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":70,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/jcmm.70941"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70941","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"type":"print","value":"1582-1838"},{"type":"electronic","value":"1582-4934"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70941"}}