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DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia

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DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia. / Gaidzik, V I; Weber, D; Paschka, P; Kaumanns, A; Krieger, S; Corbacioglu, A; Krönke, J; Kapp-Schwoerer, S; Krämer, D; Horst, H-A; Schmidt-Wolf, Ingo G H; Held, G; Kündgen, A; Ringhoffer, M; Götze, Katharina; Kindler, T; Fiedler, W; Wattad, M; Schlenk, R F; Bullinger, L; Teleanu, V; Schlegelberger, B; Thol, F; Heuser, M; Ganser, A; Döhner, H; Döhner, K.

in: LEUKEMIA, Jahrgang 32, Nr. 1, 01.2018, S. 30-37.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Gaidzik, VI, Weber, D, Paschka, P, Kaumanns, A, Krieger, S, Corbacioglu, A, Krönke, J, Kapp-Schwoerer, S, Krämer, D, Horst, H-A, Schmidt-Wolf, IGH, Held, G, Kündgen, A, Ringhoffer, M, Götze, K, Kindler, T, Fiedler, W, Wattad, M, Schlenk, RF, Bullinger, L, Teleanu, V, Schlegelberger, B, Thol, F, Heuser, M, Ganser, A, Döhner, H & Döhner, K 2018, 'DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia', LEUKEMIA, Jg. 32, Nr. 1, S. 30-37. https://doi.org/10.1038/leu.2017.200

APA

Gaidzik, V. I., Weber, D., Paschka, P., Kaumanns, A., Krieger, S., Corbacioglu, A., Krönke, J., Kapp-Schwoerer, S., Krämer, D., Horst, H-A., Schmidt-Wolf, I. G. H., Held, G., Kündgen, A., Ringhoffer, M., Götze, K., Kindler, T., Fiedler, W., Wattad, M., Schlenk, R. F., ... Döhner, K. (2018). DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia. LEUKEMIA, 32(1), 30-37. https://doi.org/10.1038/leu.2017.200

Vancouver

Gaidzik VI, Weber D, Paschka P, Kaumanns A, Krieger S, Corbacioglu A et al. DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia. LEUKEMIA. 2018 Jan;32(1):30-37. https://doi.org/10.1038/leu.2017.200

Bibtex

@article{8dfd2e16ea2a433aada75a52bcd60305,
title = "DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia",
abstract = "We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3Amut). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3Amut patients. At the time of diagnosis, DNMT3Amut transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3Amut transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3Amut transcript levels were significantly higher in BM than in blood after induction I (P=0.01), induction II (P=0.05), consolidation I (P=0.004) and consolidation II (P=0.008). With regard to the clinically relevant MRD time points, after two cycles of induction and at the end of therapy, DNMT3Amut transcript levels had no impact on the end point remission duration and overall survival. Of note, only a minority of the patients achieved RQ-PCR negativity, whereas most had constantly high DNMT3Amut transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.",
keywords = "Journal Article",
author = "Gaidzik, {V I} and D Weber and P Paschka and A Kaumanns and S Krieger and A Corbacioglu and J Kr{\"o}nke and S Kapp-Schwoerer and D Kr{\"a}mer and H-A Horst and Schmidt-Wolf, {Ingo G H} and G Held and A K{\"u}ndgen and M Ringhoffer and Katharina G{\"o}tze and T Kindler and W Fiedler and M Wattad and Schlenk, {R F} and L Bullinger and V Teleanu and B Schlegelberger and F Thol and M Heuser and A Ganser and H D{\"o}hner and K D{\"o}hner",
year = "2018",
month = jan,
doi = "10.1038/leu.2017.200",
language = "English",
volume = "32",
pages = "30--37",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia

AU - Gaidzik, V I

AU - Weber, D

AU - Paschka, P

AU - Kaumanns, A

AU - Krieger, S

AU - Corbacioglu, A

AU - Krönke, J

AU - Kapp-Schwoerer, S

AU - Krämer, D

AU - Horst, H-A

AU - Schmidt-Wolf, Ingo G H

AU - Held, G

AU - Kündgen, A

AU - Ringhoffer, M

AU - Götze, Katharina

AU - Kindler, T

AU - Fiedler, W

AU - Wattad, M

AU - Schlenk, R F

AU - Bullinger, L

AU - Teleanu, V

AU - Schlegelberger, B

AU - Thol, F

AU - Heuser, M

AU - Ganser, A

AU - Döhner, H

AU - Döhner, K

PY - 2018/1

Y1 - 2018/1

N2 - We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3Amut). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3Amut patients. At the time of diagnosis, DNMT3Amut transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3Amut transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3Amut transcript levels were significantly higher in BM than in blood after induction I (P=0.01), induction II (P=0.05), consolidation I (P=0.004) and consolidation II (P=0.008). With regard to the clinically relevant MRD time points, after two cycles of induction and at the end of therapy, DNMT3Amut transcript levels had no impact on the end point remission duration and overall survival. Of note, only a minority of the patients achieved RQ-PCR negativity, whereas most had constantly high DNMT3Amut transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.

AB - We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3Amut). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3Amut patients. At the time of diagnosis, DNMT3Amut transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3Amut transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3Amut transcript levels were significantly higher in BM than in blood after induction I (P=0.01), induction II (P=0.05), consolidation I (P=0.004) and consolidation II (P=0.008). With regard to the clinically relevant MRD time points, after two cycles of induction and at the end of therapy, DNMT3Amut transcript levels had no impact on the end point remission duration and overall survival. Of note, only a minority of the patients achieved RQ-PCR negativity, whereas most had constantly high DNMT3Amut transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.

KW - Journal Article

U2 - 10.1038/leu.2017.200

DO - 10.1038/leu.2017.200

M3 - SCORING: Journal article

C2 - 28643785

VL - 32

SP - 30

EP - 37

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 1

ER -