The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia

作者：Both Anna; Krauter Jrgen; Damm Frederik; Thol Felicitas; Goehring Gudrun; Heuser Michael; Ottmann Oliver; Luebbert Michael; Wattad Mohammed; Kanz Lothar; Schlimok Guenter; Raghavachar Aruna; Fiedler Walter; Kirchner Hartmut; Brugger Wolfram; Schlegelberger Brigitte; Heil Gerhard; Ganser Arnold; Wagner Katharina^*

来源：Annals of Hematology, 2017, 96(6): 895-904.

DOI：10.1007/s00277-017-2967-0

• Acute myeloid leukemia
• Telomerase
• Karyotype
• Gene mutations
• Prognostic factors

Hypomorphic germline variants in TERT, the gene encoding the reverse transcriptase component of the human telomerase complex, occur with a frequency of 3-5% in acute myeloid leukemia. We analyzed the clinical and prognostic impact of the most common TERTA1062T variant in younger patients with acute myeloid leukemia intensively treated within two prospective multicenter trials. Four hundred and twenty patients (age 17-60 years) were analyzed for the TERT A1062T variant by direct sequencing. Fifteen patients (3.6%) carried the TERT A1062T variant. Patients with the TERT A1062T variant had a trend towards less favorable and more intermediate 2/adverse karyotypes/genotypes according to the European Leukemia Net classification. In univariate and multivariate analysis, patients with the TERT A1062T variant had a significantly inferior overall survival compared to wild-type patients (6-year overall survival 20 vs. 41%, p = 0.005). Patients with the TERT A1062T variant showed a high rate of treatment-related mortality: 5/15 (33%) died during induction therapy or in complete remission as compared to 62/405 (15%) of the wild-type patients. In patients with the TERT variant, 14/15 (93%) suffered from non-hematological/non-infectious grade 3/4 adverse events (mostly hepatic and/or mucosal) as compared to 216/405 (53%) wild-type patients (p = 0.006). In multivariate analysis, the TERT A1062T variant was an independent risk factor predicting for adverse events during induction chemotherapy. In conclusion, the TERT A1062T variant is an independent negative prognostic factor in younger patients with acute myeloid leukemia and seems to predispose those patients to treatment-related toxicity.

• 出版日期2017-6
• 单位河北医科大学