TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs)
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- Olivier Kosmider
- Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris;
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- Véronique Gelsi-Boyer
- Laboratoire d'Oncologie Moléculaire, Centre de Recherches en Cancérologie, Inserm UMR891, Institut Paoli-Calmettes, Marseille;
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- Meyling Cheok
- Centre de Recherche Inserm 837, Institut pour la Recherche sur le Cancer de Lille (IRCL);
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- Sophie Grabar
- Faculté de Médecine René Descartes, Université Paris Descartes, Paris;
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- Véronique Della-Valle
- Faculté de Médecine René Descartes, Université Paris Descartes, Paris;
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- Françoise Picard
- Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris;
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- Franck Viguié
- Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris;
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- Bruno Quesnel
- Centre de Recherche Inserm 837, Institut pour la Recherche sur le Cancer de Lille (IRCL);
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- Odile Beyne-Rauzy
- Service de Médecine Interne, CHU Purpan, Toulouse;
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- Eric Solary
- Université de Bourgogne, Faculté de Médecine, IFR100, Inserm U866, Dijon;
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- Norbert Vey
- Service d'Hématologie, Institut Paoli Calmettes, Marseille;
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- Mathilde Hunault-Berger
- Service des Maladies du Sang, CHU, Angers;
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- Pierre Fenaux
- AP-HP, Service des Maladies du Sang, Hôpital Avicenne, Université Paris 13, Paris;
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- Véronique Mansat-De Mas
- Laboratoire d'Hématologie, CHU Purpan, Toulouse;
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- Eric Delabesse
- Laboratoire d'Hématologie, CHU Purpan, Toulouse;
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- Philippe Guardiola
- Service des Maladies du Sang, CHU, Angers;
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- Catherine Lacombe
- Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris;
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- William Vainchenker
- Inserm U790, Villejuif, Université Paris XI, Paris; and
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- Claude Preudhomme
- Centre de Recherche Inserm 837, Institut pour la Recherche sur le Cancer de Lille (IRCL);
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- François Dreyfus
- Département d'Immuno-Hématologie, Institut Cochin, Paris;
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- Olivier A. Bernard
- Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris;
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- Daniel Birnbaum
- Laboratoire d'Oncologie Moléculaire, Centre de Recherches en Cancérologie, Inserm UMR891, Institut Paoli-Calmettes, Marseille;
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- Michaëla Fontenay
- Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris;
抄録
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Blood
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Blood 114 (15), 3285-3291, 2009-10-08
American Society of Hematology