2009.08.13 – TET2 Mutation Is an Independent Favorable Prognostic Factor in Myelodysplastic Syndromes (MDS)

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2009.08.13 – TET2 Mutation Is an Independent Favorable Prognostic Factor in Myelodysplastic Syndromes (MDS)

Blood. 2009 Aug 13; Epub ahead of print, O Kosmider, V Gelsi-Boyer, M Cheok, S Grabar, V Della-Valle, F Picard, F Viguie, B Quesnel, O Beyne-Rauzy, E Solary, N Vey, M Hunault-Berger, P Fenaux, V Mansat-De Mas, E Delabesse, P Guardiola, C Lacombe, W Vainchenker, C Preudhomme, F Dreyfus, OA Bernard, D Birnbaum, M Fontenay

ABSTRACT

Among patients with Myelodysplastic Syndromes, the presence of TET2 mutations (~20% of patients) indicate good prognosis, including better 5-year survival and 3-year leukemia-free survival.

Oncogenic pathways underlying in the development of myelodysplastic syndromes (MDS) remain poorly characterized, but mutations of the TET2 gene are frequently observed. In the present work, we evaluated the prognostic impact of TET2 mutations in MDS. Frameshift, nonsense, missense mutations or defect in gene structure were identified in 22/96 patients (22.9%; [95%CI: 14.5-31.3]) patients. Mutated and unmutated patients did not significantly differ in initial clinical or hematological parameters. Five-year overall survival was 76.9.0% [95%CI: 49.2-91.3] in mutated versus 18.3% [95%CI: 4.2-41.1] in unmutated patients (p=0.005). Three-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=0.035). In univariate analysis (Cox proportional hazard model), the absence of TET2 mutation was associated with a 4.1 [95%CI: 1.4 – 12.0] fold increased risk of death (p=0.009). In multivariate analysis adjusted for age, IPSS, 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=0.005). These results indicate that TET2 mutations observed in ~20% of patients, irrespective of the WHO or FAB subtype, represent a molecular marker for good prognosis in MDS.