{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:17:27Z","timestamp":1781716647431,"version":"3.54.5"},"reference-count":33,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIL Ravenna (Italian Association for Leukemia)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Wilms\u2019 tumor gene 1 (WT1) is a critical player in acute myeloid leukemia (AML), often serving as a biomarker for measurable residual disease (MRD). The WT1 gene is overexpressed in the majority of AML cases at diagnosis, with apparently no correlation with prognosis, and in the meantime, its role in patients with low-level expression is still undefined. This study investigates the mutational landscape and clinical outcomes of AML patients with low WT1 expression at diagnosis. Methods: We analyzed 34 AML patients with low WT1 expression (WT1\/ABL1 &lt; 250) diagnosed and treated from 2013 to 2017 at three institutions. Next-generation sequencing (NGS) was employed to investigate the mutational status of 32 genes commonly mutated in AML. The presence of specific mutations, as well as clinical outcomes, was compared to the general AML population. Results: Patients with low WT1 expression showed a significantly higher mutational burden, with a median of 3.4 mutations per patient, compared to the general AML population. Notably, clonal hematopoiesis (CHIP) or myelodysplasia-related (MR) mutations, particularly in ASXL1, TET2, and SRSF2, were present in most patients with low WT1 expression. All but one case of NPM1- or FLT3-mutant AML in the low-WT1 cohort harbored more CHIP or MR mutations. Patients with low WT1 expression had an overall survival (OS) that was superimposable to the OS expected in MR AML. Conclusions: Low WT1 expression in AML is associated with a distinct and complex mutational profile, marked by frequent CHIP and MR mutations.<\/jats:p>","DOI":"10.3390\/cancers17071213","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T04:33:43Z","timestamp":1743654823000},"page":"1213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Low WT1 Expression Identifies a Subset of Acute Myeloid Leukemia with a Distinct Genotype"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1870-5554","authenticated-orcid":false,"given":"Michela","family":"Rondoni","sequence":"first","affiliation":[{"name":"UO Ematologia, Ospedale S. Maria delle Croci, Via Randi 5, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Marconi","sequence":"additional","affiliation":[{"name":"UO Ematologia, Ospedale S. Maria delle Croci, Via Randi 5, 48121 Ravenna, Italy"},{"name":"Department of Medicine and Surgery (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"U.O. Genetica Medica, AUSL della Romagna, Piazzale della Liberazione 60, 47522 Pievesestina di Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Giannini","sequence":"additional","affiliation":[{"name":"U.O. Genetica Medica, AUSL della Romagna, Piazzale della Liberazione 60, 47522 Pievesestina di Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Zuffa","sequence":"additional","affiliation":[{"name":"U.O. Genetica Medica, AUSL della Romagna, Piazzale della Liberazione 60, 47522 Pievesestina di Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Benedetta","family":"Giannini","sequence":"additional","affiliation":[{"name":"IRCSS Istituto Romagnolo per lo Studio dei Tumori \u201cDino Amadori\u201d\u2014IRST S.r.l., 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Mianulli","sequence":"additional","affiliation":[{"name":"UO Ematologia, Ospedale Infermi, Viale Luigi Settembrini 2, 47923 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Norata","sequence":"additional","affiliation":[{"name":"IRCSS Istituto Romagnolo per lo Studio dei Tumori \u201cDino Amadori\u201d\u2014IRST S.r.l., 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Monaco","sequence":"additional","affiliation":[{"name":"UO Ematologia, Ospedale Infermi, Viale Luigi Settembrini 2, 47923 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Zaccheo","sequence":"additional","affiliation":[{"name":"IRCSS Istituto Romagnolo per lo Studio dei Tumori \u201cDino Amadori\u201d\u2014IRST S.r.l., 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2731-7898","authenticated-orcid":false,"given":"Serena","family":"Rocchi","sequence":"additional","affiliation":[{"name":"UO Ematologia, Ospedale S. Maria delle Croci, Via Randi 5, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice Anna","family":"Zannetti","sequence":"additional","affiliation":[{"name":"UO Ematologia, Ospedale S. Maria delle Croci, Via Randi 5, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9848-645X","authenticated-orcid":false,"given":"Adele","family":"Santoni","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze Mediche, Chirurgiche e Neuroscienze, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-6869","authenticated-orcid":false,"given":"Claudio","family":"Graziano","sequence":"additional","affiliation":[{"name":"U.O. Genetica Medica, AUSL della Romagna, Piazzale della Liberazione 60, 47522 Pievesestina di Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Bocchia","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze Mediche, Chirurgiche e Neuroscienze, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5189-7167","authenticated-orcid":false,"given":"Francesco","family":"Lanza","sequence":"additional","affiliation":[{"name":"UO Ematologia, Ospedale S. Maria delle Croci, Via Randi 5, 48121 Ravenna, Italy"},{"name":"Department of Medicine and Surgery (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/S0140-6736(23)00108-3","article-title":"Acute myeloid leukaemia","volume":"401","author":"DiNardo","year":"2023","journal-title":"Lancet"},{"key":"ref_2","first-page":"926","article-title":"Prognostic implications of Wilms\u2019 tumor gene (WT1) expression in patients with de novo acute myeloid leukemia","volume":"89","author":"Cervera","year":"2004","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1200\/JCO.2005.03.5303","article-title":"High WT1 expression after induction therapy predicts high risk of relapse and death in pediatric acute myeloid leukemia","volume":"24","author":"Lapillonne","year":"2006","journal-title":"J. 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