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| Item Type: | Article |
|---|---|
| Title: | Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation |
| Creators Name: | Cocciardi, S. and Dolnik, A. and Kapp-Schwoerer, S. and Rücker, F.G. and Lux, S. and Blätte, T.J. and Skambraks, S. and Krönke, J. and Heidel, F.H. and Schnöder, T.M. and Corbacioglu, A. and Gaidzik, V.I. and Paschka, P. and Teleanu, V. and Göhring, G. and Thol, F. and Heuser, M. and Ganser, A. and Weber, D. and Sträng, E. and Kestler, H.A. and Döhner, H. and Bullinger, L. and Döhner, K. |
| Abstract: | Mutations in the nucleophosmin 1 (NPM1) gene are considered founder mutations in the pathogenesis of acute myeloid leukemia (AML). To characterize the genetic composition of NPM1 mutated (NPM1(mut)) AML, we assess mutation status of five recurrently mutated oncogenes in 129 paired NPM1(mut) samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1(mut) loss (n = 11). To better understand these NPM1(mut) loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1(mut) loss patients (pts) feature distinct mutational patterns that share almost no somatic mutation with the corresponding diagnosis sample and impact different signaling pathways. In contrast, profiles of pts with persistent NPM1(mut) are reflected by a high overlap of mutations between diagnosis and relapse. Our findings confirm that relapse often originates from persistent leukemic clones, though NPM1(mut) loss cases suggest a second “de novo” or treatment-associated AML (tAML) as alternative cause of relapse. |
| Keywords: | Acute Myeloid Leukemia, Clonal Evolution, DNA Mutational Analysis, Exome Sequencing, Local Neoplasm Recurrence, Mutation, Nuclear Proteins, Nucleophosmin, Second Primary Neoplasms |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 10 |
| Number: | 1 |
| Page Range: | 2031 |
| Date: | 2 May 2019 |
| Official Publication: | https://doi.org/10.1038/s41467-019-09745-2 |
| PubMed: | View item in PubMed |
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