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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3285-3291. Prepublished online as a Blood First Edition Paper on August 7, 2009; DOI 10.1182/blood-2009-04-215814. This Article Full Text Full Text (PDF) Supplemental Appendix, Table, and Figures All Versions of this Article: blood-2009-04-215814v1 114/15/3285    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Kosmider, O. Articles by Fontenay, M. PubMed PubMed Citation Articles by Kosmider, O. Articles by Fontenay, M. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs) Olivier Kosmider15,*, Véronique Gelsi-Boyer6,*, Meyling Cheok7,8, Sophie Grabar5,9, Véronique Della-Valle5,10, Françoise Picard1,5, Franck Viguié1,5, Bruno Quesnel7,11, Odile Beyne-Rauzy12, Eric Solary13, Norbert Vey14, Mathilde Hunault-Berger15, Pierre Fenaux16, Véronique Mansat-De Mas17, Eric Delabesse17, Philippe Guardiola15, Catherine Lacombe15, William Vainchenker18, Claude Preudhomme7,8, François Dreyfus25,19, Olivier A. Bernard1,5,10, Daniel Birnbaum6, Michaëla Fontenay15, and on behalf of the Groupe Francophone des Myélodysplasies 1 Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris; 2 Département d'Immuno-Hématologie, Institut Cochin, Paris; 3 Inserm U567, Paris; 4 Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8104, Paris; 5 Faculté de Médecine René Descartes, Université Paris Descartes, Paris; 6 Laboratoire d'Oncologie Moléculaire, Centre de Recherches en Cancérologie, Inserm UMR891, Institut Paoli-Calmettes, Marseille; 7 Centre de Recherche Inserm 837, Institut pour la Recherche sur le Cancer de Lille (IRCL); 8 Laboratoire d'Hématologie, CHRU, Lille; 9 AP-HP, Département de Biostatistiques et d'Epidémiologie, Hôpital Cochin, Paris; 10 Inserm E0120, Université Paris Descartes, Paris; 11 Service des Maladies du Sang, Hôpital Huriez, CHRU, Lille; 12 Service de Médecine Interne, CHU Purpan, Toulouse; 13 Université de Bourgogne, Faculté de Médecine, IFR100, Inserm U866, Dijon; 14 Service d'Hématologie, Institut Paoli Calmettes, Marseille; 15 Service des Maladies du Sang, CHU, Angers; 16 AP-HP, Service des Maladies du Sang, Hôpital Avicenne, Université Paris 13, Paris; 17 Laboratoire d'Hématologie, CHU Purpan, Toulouse; 18 Inserm U790, Villejuif, Université Paris XI, Paris; and 19 AP-HP, Unité Fonctionnelle d'Hématologie, Département de Médecine Interne, Hôpital Cochin, Paris, France 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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