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| Item Type: | Article |
|---|---|
| Title: | DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia |
| Creators Name: | Gaidzik, V.I. and Weber, D. and Paschka, P. and Kaumanns, A. and Krieger, S. and Corbacioglu, A. and Krönke, J. and Kapp-Schwoerer, S. and Krämer, D. and Horst, H.A. and Schmidt-Wolf, I. and Held, G. and Kündgen, A. and Ringhoffer, M. and Götze, K. and Kindler, T. and Fiedler, W. and Wattad, M. and Schlenk, R.F. and Bullinger, L. and Teleanu, V. and Schlegelberger, B. and Thol, F. and Heuser, M. and Ganser, A. and Döhner, H. and Döhner, K. |
| 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). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3A patients. At the time of diagnosis, DNMT3A 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 transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3A 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 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 transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission. |
| Keywords: | DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, Hematopoiesis, Acute Myeloid Leukemia, Mutation, Residual Neoplasm, Residual Neoplasm, Prognosis |
| Source: | Leukemia |
| ISSN: | 1476-5551 |
| Publisher: | Nature Publishing Group |
| Volume: | 32 |
| Number: | 1 |
| Page Range: | 30-37 |
| Date: | January 2018 |
| Official Publication: | https://doi.org/10.1038/leu.2017.200 |
| PubMed: | View item in PubMed |
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