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ABSTRACT We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring _DNA methyltransferase 3A-_R882H/-R882C mutations
(_DNMT3A_mut). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 _DNMT3A_mut patients. At the time of diagnosis, _DNMT3A_mut 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) _DNMT3A_mut transcript
levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. _DNMT3A_mut 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, _DNMT3A_mut 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 _DNMT3A_mut transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.
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support SIMILAR CONTENT BEING VIEWED BY OTHERS GENOMIC AND TRANSCRIPTOMIC DETERMINANTS OF CLINICAL OUTCOMES IN PATIENTS WITH AML AND _DNMT3A_ MUTATIONS Article Open access 20 May 2025
MULTI-TARGET MEASURABLE RESIDUAL DISEASE ASSESSED BY ERROR-CORRECTED SEQUENCING IN PATIENTS WITH ACUTE MYELOID LEUKEMIA: AN ALFA STUDY Article Open access 13 June 2024 _ASXL1_ MUTATIONS
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Med_ 2016; 374: 2209–2221. Article CAS Google Scholar Download references ACKNOWLEDGEMENTS This work was supported in part by grants 01GI9981 and 01KG0605 from the German
Bundesministerium für Bildung und Forschung (BMBF), grant 109675 from the Deutsche Krebshilfe and the Sonderforschungsbereich (SFB) 1074 funded by the Deutsche Forschungsgemeinschaft (SFB
1074, projects B3 and B4). VG is a grant recipient of the Else-Kröner-Forschungskolleg; LB and MH are Heisenberg Professors of the Deutsche Forschungsgemeinschaft (DFG, BU 1339/3-1 and HE
5240-6-1). AMLSG treatment trials were in part supported by Pfizer and Amgen. We are grateful to all members of the German-Austrian AML Study Group (AMLSG) for their participation in this
study and providing patient samples; a list of participating institutions and investigators is provided in the Supplementary Appendix. AUTHOR CONTRIBUTIONS VIG, DW, RFS, KD and HD designed
the research; VIG, PP, AK, SK, AC, JK and SKS performed experiments; VIG, VT, PP, AK, SK, AC, JK, SKS and KD analyzed the results; DW and RFS performed statistical analyses; DK, HAH, ISW,
GH, AK, MR, KG, TK, WF, MW, LB, VT, BS, FT, MH, AG, RFS, HD and KD accrued patients and provided material; VIG, DW, HD and KD wrote the paper. AUTHOR INFORMATION Author notes * A complete
list of the members of the German-Austrian Acute Myeloid Leukemia Study Group (AMLSG) is provided in Supplementary Information. AUTHORS AND AFFILIATIONS * Universitätsklinikum Ulm, Ulm,
Germany V I Gaidzik, D Weber, P Paschka, A Kaumanns, S Krieger, A Corbacioglu, J Krönke, S Kapp-Schwoerer, R F Schlenk, L Bullinger, V Teleanu, H Döhner & K Döhner * Klinikum Oldenburg,
Oldenburg, Germany D Krämer * Universitätsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany H-A Horst * Universitätsklinikum Bonn, Bonn, Germany I Schmidt-Wolf * Universitätsklinikum
des Saarlandes, Homburg, Germany G Held * Universitätsklinikum Düsseldorf, Düsseldorf, Germany A Kündgen * Städtisches Klinikum Karlsruhe GmbH, Karlsruhe, Germany M Ringhoffer * Klinikum
rechts der Isar der Technischen Universität München, München, Germany K Götze * Universitätsmedizin Mainz, Mainz, Germany T Kindler * Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
W Fiedler * Kliniken Essen Süd, Ev. Krankenhaus Essen-Werden gGmbH, Essen, Germany M Wattad * Medizinische Hochschule Hannover, Hannover, Germany B Schlegelberger, F Thol, M Heuser & A
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INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Presented in abstract form at the 57th Annual Meeting of the American Society of Hematology, Orlando, FL, USA on
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and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gaidzik, V., Weber, D., Paschka, P. _et al._ _DNMT3A_ mutant transcript levels persist in remission and do not predict outcome in
patients with acute myeloid leukemia. _Leukemia_ 32, 30–37 (2018). https://doi.org/10.1038/leu.2017.200 Download citation * Received: 08 June 2017 * Accepted: 13 June 2017 * Published: 23
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