{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:47:04Z","timestamp":1790948824938,"version":"4.1.0"},"reference-count":63,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Several genomic subsets of\n              <jats:italic>NPM1<\/jats:italic>\n              mutations with varying sequences (type A, B, D, etc) have been identified. Despite molecular heterogeneity,\n              <jats:italic>NPM1<\/jats:italic>\n              mutations cumulatively portend a more favorable outcome, but biology and prognostic implications of different genomic subsets have not been extensively studied. In this multicentric study, we investigated the impact of\n              <jats:italic>NPM1<\/jats:italic>\n              genotypes on patient's outcomes and interrogated the underlying biology of the different subtypes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>MATERIALS AND METHODS<\/jats:title>\n            <jats:p>\n              Of more than 4,000 patients enrolled in multiple pediatric cooperative (AIEOP, BFM, ELAM02, NOPHO, DCOG, and COG trials), or adult (SWOG) trials, 348 pediatric and 75 adult AML patients with known\n              <jats:italic>NPM1<\/jats:italic>\n              genotype and available outcome were selected for this study. Diverse\n              <jats:italic>NPM1<\/jats:italic>\n              variants were correlated with the probabilities of overall survival (OS) and event-free survival. Nuclear localization and translational efficiency of the\n              <jats:italic>NPM1<\/jats:italic>\n              variants was studied.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Evaluation of clinical outcome on the basis of\n              <jats:italic>NPM1<\/jats:italic>\n              genotypes showed that patients with type A, B, and other rare variants had similarly favorable outcomes, whereas those with type D had a significantly worse outcome (OS of 63% for type D\n              <jats:italic>v<\/jats:italic>\n              86% for type non-D,\n              <jats:italic>P<\/jats:italic>\n              = .005). Multivariate analysis confirmed type D as an independent prognostic factor associated with inferior OS (hazard ratio, 3;\n              <jats:italic>P<\/jats:italic>\n              = .005). In vitro, we demonstrated that in type D versus type A synonymous variants, codon optimality plays major roles in determining gene expression levels, and translation efficiency, which resulted in a more expressed\n              <jats:italic>NPM1-D<\/jats:italic>\n              mRNA and protein, mediating peculiar mitochondrial gene expression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              The evaluation of specific\n              <jats:italic>NPM1<\/jats:italic>\n              genotypes identified AML patients with type D mutations being significantly associated with inferior outcomes, suggesting a reclassification of D cases to higher-risk groups.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-24-01715","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T21:10:56Z","timestamp":1733173856000},"page":"972-984","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Influence of Nucleophosmin (\n            <i>NPM1<\/i>\n            ) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-0555","authenticated-orcid":true,"given":"Claudia","family":"Tregnago","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health, Onco-hematology Lab and Clinic, University of Padova, Padova, 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Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Sonneveld","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-3522","authenticated-orcid":true,"given":"Jonas","family":"Abrahamsson","sequence":"additional","affiliation":[{"name":"Institution for Clinical Sciences, Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-8519","authenticated-orcid":true,"given":"Linda","family":"Fogelstrand","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, 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