title: TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs).
abstract: 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.
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris, France.
authors: Olivier
authors: O
authors: Kosmider
authors: Véronique
authors: V
authors: Gelsi-Boyer
authors: Meyling
authors: M
authors: Cheok
authors: Sophie
authors: S
authors: Grabar
authors: Véronique
authors: V
authors: Della-Valle
authors: Françoise
authors: F
authors: Picard
authors: Franck
authors: F
authors: Viguié
authors: Bruno
authors: B
authors: Quesnel
authors: Odile
authors: O
authors: Beyne-Rauzy
authors: Eric
authors: E
authors: Solary
authors: Norbert
authors: N
authors: Vey
authors: Mathilde
authors: M
authors: Hunault-Berger
authors: Pierre
authors: P
authors: Fenaux
authors: Véronique
authors: V
authors: Mansat-De Mas
authors: Eric
authors: E
authors: Delabesse
authors: Philippe
authors: P
authors: Guardiola
authors: Catherine
authors: C
authors: Lacombe
authors: William
authors: W
authors: Vainchenker
authors: Claude
authors: C
authors: Preudhomme
authors: François
authors: F
authors: Dreyfus
authors: Olivier A
authors: OA
authors: Bernard
authors: Daniel
authors: D
authors: Birnbaum
authors: Michaëla
authors: M
authors: Fontenay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D049308:Dioxygenases; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality*; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human