期刊
JOURNAL OF CLINICAL ONCOLOGY
卷 26, 期 28, 页码 4595-4602出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2007.15.2058
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资金
- National Cancer Institute, Bethesda [CA77658, CA101140, CA114725, CA31946, CA33601, CA16058]
- Coleman Leukemia Research Foundation
- NATIONAL CANCER INSTITUTE [U10CA033601, U10CA077298, U10CA021060, U10CA011789, U10CA004457, U10CA047642, U10CA047559, U10CA052784, U10CA060138, U10CA031946, U10CA002599, U10CA026806, U10CA007968, U10CA041287, U10CA035421, U10CA012046, U10CA101140, U10CA037135, U10CA077597, U10CA004326, U24CA114725, U10CA047577, U10CA077406, U10CA077658, U10CA035279, U10CA074811, U10CA047555, U10CA032291, U10CA012449, U10CA008025, U10CA011028, U10CA035406, P30CA016058, U10CA003927, U10CA045418, U10CA016450] Funding Source: NIH RePORTER
Purpose To analyze the prognostic impact of Wilms' tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods 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. Results 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 < .001; 3-year rates, 13% v 50%) and overall survival (OS; P < .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(negative)/NPM1(mutated) as low risk v FLT3-ITD(positive) and/or NPM1(wild-type) as high risk). WT1 mutations also independently predicted worse OS (P < .001; HR = 3.2) when controlling for CEBPA mutational status, FLT3-ITD/NPM1 molecular-risk group, and white blood cell count. Conclusion 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.
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