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Prevalence and prognostic impact of NPM1mutations in 1485 adult patients with acute myeloid leukemia (AML)
- Source :
- Blood; May 2006, Vol. 107 Issue: 10 p4011-4020, 10p
- Publication Year :
- 2006
-
Abstract
- 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 NPM1exon 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, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1mutations were most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%) compared with 58 of 686 with karyotype abnormalities (8.5%; P< .001) and were significantly associated with several clinical parameters (high bone marrow [BM] blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P< .001). The analysis of the clinical impact in 4 groups (NPM1and FLT3-ITD single mutants, double mutants, and wild-type [wt] for both) revealed that patients having only an NPM1mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse. In conclusion, NPM1mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1appears to identify patients with improved response toward treatment.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 107
- Issue :
- 10
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs56980988
- Full Text :
- https://doi.org/10.1182/blood-2005-08-3167