Dnmt3a mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia

Dnmt3a mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia

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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


Ganser Authors * V I Gaidzik View author publications You can also search for this author inPubMed Google Scholar * D Weber View author publications You can also search for this author


inPubMed Google Scholar * P Paschka View author publications You can also search for this author inPubMed Google Scholar * A Kaumanns View author publications You can also search for this


author inPubMed Google Scholar * S Krieger View author publications You can also search for this author inPubMed Google Scholar * A Corbacioglu View author publications You can also search


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can also search for this author inPubMed Google Scholar * I Schmidt-Wolf View author publications You can also search for this author inPubMed Google Scholar * G Held View author


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author inPubMed Google Scholar CONSORTIA FOR THE GERMAN-AUSTRIAN ACUTE MYELOID LEUKEMIA STUDY GROUP (AMLSG) CORRESPONDING AUTHOR Correspondence to K Döhner. ETHICS DECLARATIONS COMPETING


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


6 December 2015. Supplementary Information accompanies this paper on the Leukemia website SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION (DOCX 1127 KB) RIGHTS AND PERMISSIONS Reprints


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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