TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs).
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.
Kosmider
Olivier
O
Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpital Cochin-Hôtel-Dieu, Paris, France.
Gelsi-Boyer
Véronique
V
Cheok
Meyling
M
Grabar
Sophie
S
Della-Valle
Véronique
V
Picard
Françoise
F
Viguié
Franck
F
Quesnel
Bruno
B
Beyne-Rauzy
Odile
O
Solary
Eric
E
Vey
Norbert
N
Hunault-Berger
Mathilde
M
Fenaux
Pierre
P
Mansat-De Mas
Véronique
V
Delabesse
Eric
E
Guardiola
Philippe
P
Lacombe
Catherine
C
Vainchenker
William
W
Preudhomme
Claude
C
Dreyfus
François
F
Bernard
Olivier A
OA
Birnbaum
Daniel
D
Fontenay
Michaëla
M
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
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human