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

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The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia. / Both, Anna; Krauter, Jürgen; Damm, Frederik; Thol, Felicitas; Göhring, Gudrun; Heuser, Michael; Ottmann, Oliver; Lübbert, Michael; Wattad, Mohammed; Kanz, Lothar; Schlimok, Günter; Raghavachar, Aruna; Fiedler, Walter; Kirchner, Hartmut; Brugger, Wolfram; Schlegelberger, Brigitte; Heil, Gerhard; Ganser, Arnold; Wagner, Katharina.

In: ANN HEMATOL, Vol. 96, No. 6, 06.2017, p. 895-904.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Both, A, Krauter, J, Damm, F, Thol, F, Göhring, G, Heuser, M, Ottmann, O, Lübbert, M, Wattad, M, Kanz, L, Schlimok, G, Raghavachar, A, Fiedler, W, Kirchner, H, Brugger, W, Schlegelberger, B, Heil, G, Ganser, A & Wagner, K 2017, 'The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia', ANN HEMATOL, vol. 96, no. 6, pp. 895-904. https://doi.org/10.1007/s00277-017-2967-0

APA

Both, A., Krauter, J., Damm, F., Thol, F., Göhring, G., Heuser, M., Ottmann, O., Lübbert, M., Wattad, M., Kanz, L., Schlimok, G., Raghavachar, A., Fiedler, W., Kirchner, H., Brugger, W., Schlegelberger, B., Heil, G., Ganser, A., & Wagner, K. (2017). The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia. ANN HEMATOL, 96(6), 895-904. https://doi.org/10.1007/s00277-017-2967-0

Vancouver

Both A, Krauter J, Damm F, Thol F, Göhring G, Heuser M et al. The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia. ANN HEMATOL. 2017 Jun;96(6):895-904. https://doi.org/10.1007/s00277-017-2967-0

Bibtex

@article{413efffe943941e3a5764c52576a70a4,
title = "The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia",
abstract = "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 TERT A1062T 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.",
keywords = "Journal Article",
author = "Anna Both and J{\"u}rgen Krauter and Frederik Damm and Felicitas Thol and Gudrun G{\"o}hring and Michael Heuser and Oliver Ottmann and Michael L{\"u}bbert and Mohammed Wattad and Lothar Kanz and G{\"u}nter Schlimok and Aruna Raghavachar and Walter Fiedler and Hartmut Kirchner and Wolfram Brugger and Brigitte Schlegelberger and Gerhard Heil and Arnold Ganser and Katharina Wagner",
year = "2017",
month = jun,
doi = "10.1007/s00277-017-2967-0",
language = "English",
volume = "96",
pages = "895--904",
journal = "ANN HEMATOL",
issn = "0939-5555",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - The hypomorphic TERT A1062T variant is associated with increased treatment-related toxicity in acute myeloid leukemia

AU - Both, Anna

AU - Krauter, Jürgen

AU - Damm, Frederik

AU - Thol, Felicitas

AU - Göhring, Gudrun

AU - Heuser, Michael

AU - Ottmann, Oliver

AU - Lübbert, Michael

AU - Wattad, Mohammed

AU - Kanz, Lothar

AU - Schlimok, Günter

AU - Raghavachar, Aruna

AU - Fiedler, Walter

AU - Kirchner, Hartmut

AU - Brugger, Wolfram

AU - Schlegelberger, Brigitte

AU - Heil, Gerhard

AU - Ganser, Arnold

AU - Wagner, Katharina

PY - 2017/6

Y1 - 2017/6

N2 - 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 TERT A1062T 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.

AB - 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 TERT A1062T 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.

KW - Journal Article

U2 - 10.1007/s00277-017-2967-0

DO - 10.1007/s00277-017-2967-0

M3 - SCORING: Journal article

C2 - 28331964

VL - 96

SP - 895

EP - 904

JO - ANN HEMATOL

JF - ANN HEMATOL

SN - 0939-5555

IS - 6

ER -