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
Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris, France.
Blood. 2009 Oct 8;114(15):3285-91. doi: 10.1182/blood-2009-04-215814. Epub 2009 Aug 7.
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.
骨髓增生异常综合征（MDS）发生发展的致癌途径仍未得到充分表征，但经常观察到10-11易位2（TET2）基因的突变。在本研究中，我们评估了TET2突变对MDS的预后影响。在96例患者中的22例（22.9%）中鉴定出移码突变、无义突变、错义突变或基因结构缺陷（95%置信区间[CI]，14.5 - 31.3例患者）。突变患者和未突变患者在初始临床或血液学参数上无显著差异。突变患者的5年总生存率为76.9%（95% CI，49.2% - 91.3%），而未突变患者为18.3%（95% CI，4.2% - 41.1%）（P = 0.005）。突变患者的3年无白血病生存率为89.3%（95% CI，63.1% - 97.0%），未突变患者为63.7%（95% CI，48.2% - 75.4%）（P = 0.035）。在单因素分析（Cox比例风险模型）中，TET2突变的缺失与死亡风险增加4.1倍（95% CI，1.4 - 12.0倍）相关（P = 0.009）。在根据年龄、国际预后评分系统和输血需求进行调整的多因素分析中，TET2突变的存在仍然是预后良好的独立因素（风险比，5.2；95% CI，1.6 - 16.3；P = 0.005）。这些结果表明，在约20%的患者中观察到的TET2突变，无论世界卫生组织或法美英亚型如何，都是MDS预后良好的分子标志物。
