Regular Manuscript Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML) Short title: NPM1 mutations in AML - Scientific Section: NEOPLASIA
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چکیده
Mutations of the Nucleophosmin (NPM1) gene have recently been described in patients with AML. To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4-bp insert was detected in 408/1485 patients (27.5%). Sequence analysis revealed known mutations (Type A, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1-mutations were most prevalent in patients with normal karyotype (NK) (324/709; 45.7%) compared to 58/686 with karyotype abnormalities (8.5%; P<.0001), and were significantly associated with several clinical parameters (high BM blasts, high WBC and platelet counts, female gender). NPM1 alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8% vs. NPM1-wt/FLT3ITD: 19.9%; p<.001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single mutants, double mutants and wt for both) revealed that patients having only an NPM1-mutation had a significantly better overall and disease free survival and a lower cumulative incidence of relapse. In conclusion, NPM1-mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response towards treatment. E-mail corresponding author: [email protected] only. For personal use at PENN STATE UNIVERSITY on February 20, 2013. bloodjournal.hematologylibrary.org From THIEDE et al 3 NPM1 MUTATIONS IN AML
منابع مشابه
Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML).
Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, ...
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