{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:15:06Z","timestamp":1790864106827,"version":"4.1.0"},"reference-count":50,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To analyze the prognostic impact of Wilms\u2019 tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML). <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> We studied 196 adults younger than 60 years with newly diagnosed primary CN-AML, who were treated similarly on Cancer and Leukemia Group B (CALGB) protocols 9621 and 19808, for WT1 mutations in exons 7 and 9. The patients also were assessed for the presence of FLT3 internal tandem duplications (FLT3-ITD), FLT3 tyrosine kinase domain mutations (FLT3-TKD), MLL partial tandem duplications (MLL-PTD), NPM1 and CEBPA mutations, and for the expression levels of ERG and BAALC. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Twenty-one patients (10.7%) harbored WT1 mutations. Complete remission rates were not significantly different between patients with WT1 mutations and those with unmutated WT1 (P = .36; 76% v 84%). Patients with WT1 mutations had worse disease-free survival (DFS; P &lt; .001; 3-year rates, 13% v 50%) and overall survival (OS; P &lt; .001; 3-year rates, 10% v 56%) than patients with unmutated WT1. In multivariable analyses, WT1 mutations independently predicted worse DFS (P = .009; hazard ratio [HR] = 2.7) when controlling for CEBPA mutational status, ERG expression level, and FLT3-ITD\/NPM1 molecular-risk group (ie, FLT3-ITD<jats:sup>negative<\/jats:sup>\/NPM1<jats:sup>mutated<\/jats:sup> as low risk v FLT3-ITD<jats:sup>positive<\/jats:sup> and\/or NPM1<jats:sup>wild-type<\/jats:sup> as high risk). WT1 mutations also independently predicted worse OS (P &lt; .001; HR = 3.2) when controlling for CEBPA mutational status, FLT3-ITD\/NPM1 molecular-risk group, and white blood cell count. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> We report the first evidence that WT1 mutations independently predict extremely poor outcome in intensively treated, younger patients with CN-AML. Future trials should include testing for WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2007.15.2058","type":"journal-article","created":{"date-parts":[[2008,6,17]],"date-time":"2008-06-17T01:35:31Z","timestamp":1213666531000},"page":"4595-4602","source":"Crossref","is-referenced-by-count":207,"title":["Wilms\u2019 Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study"],"prefix":"10.1200","volume":"26","author":[{"given":"Peter","family":"Paschka","sequence":"first","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; and Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Pathology; The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham; and Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; Department of Hematology and Oncology, Charit\u00e9 University Hospital, Campus Benjamin Franklin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Marcucci","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; and Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Pathology; The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham; and Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; Department of Hematology and Oncology, Charit\u00e9 University Hospital, Campus Benjamin Franklin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Ruppert","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; and Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Pathology; The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham; and Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; Department of Hematology and Oncology, Charit\u00e9 University Hospital, Campus Benjamin Franklin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P.","family":"Whitman","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; and Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Pathology; The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham; and Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; Department of Hematology and Oncology, Charit\u00e9 University Hospital, Campus Benjamin Franklin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Mr\u00f3zek","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; and Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Pathology; The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham; and Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; Department of Hematology and Oncology, Charit\u00e9 University Hospital, Campus Benjamin Franklin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Maharry","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; and Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Pathology; The Ohio State University, Columbus, OH; Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham; and Section on Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC; Department of Hematology and Oncology, Charit\u00e9 University Hospital, Campus Benjamin Franklin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Langer","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, Department of Internal Medicine; 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