TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs)

Oncogenic pathways underlying in the development of myelodysplastic syndromes (MDS) remain poorly characterized, but mutations of the ten-eleven translocation 2 (TET2) gene are frequently observed. In the present work, we evaluated the prognostic impact of TET2 mutations in MDS. Frameshift, nonsense...

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Published in:Blood Vol. 114; no. 15; p. 3285
Main Authors: Kosmider, Olivier, Gelsi-Boyer, Véronique, Cheok, Meyling, Grabar, Sophie, Della-Valle, Véronique, Picard, Françoise, Viguié, Franck, Quesnel, Bruno, Beyne-Rauzy, Odile, Solary, Eric, Vey, Norbert, Hunault-Berger, Mathilde, Fenaux, Pierre, Mansat-De Mas, Véronique, Delabesse, Eric, Guardiola, Philippe, Lacombe, Catherine, Vainchenker, William, Preudhomme, Claude, Dreyfus, François, Bernard, Olivier A, Birnbaum, Daniel, Fontenay, Michaëla
Format: Journal Article
Language:English
Published: United States 08.10.2009
Subjects:
Aged
Aged, 80 and over
Disease-Free Survival
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Female
Follow-Up Studies
Genetic Markers
Humans
Male
Middle Aged
Mutation
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - mortality
Predictive Value of Tests
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Risk Factors
Survival Rate
ISSN:1528-0020, 1528-0020
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Summary:Oncogenic pathways underlying in the development of myelodysplastic syndromes (MDS) remain poorly characterized, but mutations of the ten-eleven translocation 2 (TET2) gene are frequently observed. In the present work, we evaluated the prognostic impact of TET2 mutations in MDS. Frameshift, nonsense, missense mutations, or defects in gene structure were identified in 22 (22.9%) of 96 patients (95% confidence interval [CI], 14.5-31.3 patients). Mutated and unmutated patients did not significantly differ in initial clinical or hematologic parameters. The 5-year OS was 76.9% (95% CI, 49.2%-91.3%) in mutated versus 18.3% (95% CI, 4.2%-41.1%) in unmutated patients (P = .005). The 3-year leukemia-free survival was 89.3% (95% CI, 63.1%-97.0%) in mutated versus 63.7% (95% CI, 48.2%-75.4%) in unmutated patients (P = .035). In univariate analysis (Cox proportional hazard model), the absence of TET2 mutation was associated with a 4.1-fold (95% CI, 1.4-12.0-fold) increased risk of death (P = .009). In multivariate analysis adjusted for age, International Prognostic Scoring System, and transfusion requirement, the presence of TET2 mutation remained an independent factor of favorable prognosis (hazard ratio, 5.2; 95% CI, 1.6-16.3; P = .005). These results indicate that TET2 mutations observed in approximately 20% of patients, irrespective of the World Health Organization or French-American-British subtype, represent a molecular marker for good prognosis in MDS.
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ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2009-04-215814