{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:45:41Z","timestamp":1788983141291,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Splicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real\u2010life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia\u2010related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML\u2010related genes by next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We showed that <jats:italic>TET2<\/jats:italic>, <jats:italic>SETBP1<\/jats:italic>, <jats:italic>ASXL1<\/jats:italic>, <jats:italic>EZH2<\/jats:italic>, <jats:italic>RUNX1<\/jats:italic>, <jats:italic>SRSF2<\/jats:italic>, <jats:italic>DNMT3A<\/jats:italic>, and <jats:italic>IDH1\/2<\/jats:italic> were commonly mutated. MDS patients also showed a high genetic complexity, especially for <jats:italic>SETBP1<\/jats:italic>. Moreover, the presence of <jats:italic>SETBP1<\/jats:italic> wild\u2010type or two or more simultaneous VUS variants identified a subgroup of AML and MDS patients with better outcome, while the presence of single <jats:italic>SETBP1<\/jats:italic> VUS variant was related to a worse prognosis, regardless <jats:italic>TET2<\/jats:italic> mutational status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusions, we linked both pathogenic and VUS variants in AML\u2010related genes to clonal hematopoiesis; therefore, we proposed to consider those variants as prognostic markers in leukemia and myelodysplasia. However, further studies in larger prospective cohorts are required to validate our results.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14069","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T06:03:49Z","timestamp":1690524229000},"page":"729-741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-6848","authenticated-orcid":false,"given":"Valentina","family":"Giudice","sequence":"first","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"},{"name":"Department of Medicine, Surgery, and Dentistry University of Salerno  Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6613-2370","authenticated-orcid":false,"given":"Bianca","family":"Serio","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3154-734X","authenticated-orcid":false,"given":"Santa","family":"Errichiello","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, CEINGE\u2010Biotecnologie Avanzate University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2778-8127","authenticated-orcid":false,"given":"Idalucia","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5842-5155","authenticated-orcid":false,"given":"Alessandra","family":"Galdiero","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, CEINGE\u2010Biotecnologie Avanzate University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-6479","authenticated-orcid":false,"given":"Angela","family":"Bertolini","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6682-6645","authenticated-orcid":false,"given":"Roberta","family":"Visconti","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, CEINGE\u2010Biotecnologie Avanzate University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2590-0529","authenticated-orcid":false,"given":"Danilo","family":"De Novellis","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"},{"name":"Department of Medicine, Surgery, and Dentistry University of Salerno  Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4165-8646","authenticated-orcid":false,"given":"Roberto","family":"Guariglia","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7063-970X","authenticated-orcid":false,"given":"Serena","family":"Luponio","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4921-1081","authenticated-orcid":false,"given":"Denise","family":"Morini","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1972-6336","authenticated-orcid":false,"given":"Anna Maria","family":"Della Corte","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0365-5143","authenticated-orcid":false,"given":"Anna Maria","family":"Sessa","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0081-0914","authenticated-orcid":false,"given":"Francesco","family":"Verdesca","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0899-7219","authenticated-orcid":false,"given":"Maddalena","family":"Langella","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7021-0367","authenticated-orcid":false,"given":"Barbara","family":"Izzo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, CEINGE\u2010Biotecnologie Avanzate University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5861-8984","authenticated-orcid":false,"given":"Carmine","family":"Selleri","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center University Hospital \u201cSan Giovanni di Dio e Ruggi d'Aragona\u201d  Salerno Italy"},{"name":"Department of Medicine, Surgery, and Dentistry University of Salerno  Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","first-page":"387","article-title":"WT1 expression levels combined with flow cytometry blast counts for risk stratification of acute myeloid leukemia and myelodysplastic syndromes","volume":"9","author":"Giudice V","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000524952"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-6-50"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2021.101276"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.248955"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13143380"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-08-518886"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01659"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cger.2019.03.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-794362"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-631747"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01823"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.023"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022008141"},{"issue":"2","key":"e_1_2_11_16_1","first-page":"121","article-title":"Genetic landscape of acute myeloid leukemia interrogated by next\u2010generation sequencing: a large cancer center experience","volume":"15","author":"Hussaini MO","year":"2018","journal-title":"Cancer Genomics Proteomics"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2022.11.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.118.002169"},{"issue":"6","key":"e_1_2_11_19_1","article-title":"Nordic guidelines for germline predisposition to myeloid neoplasms in adults: recommendations for genetic diagnosis, clinical management and follow\u2010up","volume":"3","author":"Baliakas P","year":"2019","journal-title":"Hema"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.11.002"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e11998"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1052060"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0396-7"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01784"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2022.101033"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24055018"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-10-844621"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.191536"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.989483"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065734"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280801"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3467"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34481"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jha2.264"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04462-8"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-388710"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.200"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.813430"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9780"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-0278-0"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12491"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23611"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.630754"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0060-9"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18729-6"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-274704"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5602-8"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0150-9"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0151"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-582809"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.1824"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.01.011"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2015.08.012"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.14069","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T08:47:39Z","timestamp":1704530859000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.14069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/ejh.14069"],"URL":"https:\/\/doi.org\/10.1111\/ejh.14069","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]},"assertion":[{"value":"2023-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}