Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation

Sibylle Cocciardi, Anna Dolnik, Silke Kapp-Schwoerer, Frank G. Rücker, Susanne Lux, Tamara J. Blätte, Sabrina Skambraks, Jan Krönke, Florian H. Heidel, Tina M. Schnöder, Andrea Corbacioglu, Verena I. Gaidzik, Peter Paschka, Veronica Teleanu, Gudrun Göhring, Felicitas Thol, Michael Heuser, Arnold Ganser, Daniela Weber, Eric Sträng, Hans A. Kestler, Hartmut Döhner, Lars Bullinger () and Konstanze Döhner ()
Additional contact information
Sibylle Cocciardi: University Hospital of Ulm
Anna Dolnik: University Hospital of Ulm
Silke Kapp-Schwoerer: University Hospital of Ulm
Frank G. Rücker: University Hospital of Ulm
Susanne Lux: University Hospital of Ulm
Tamara J. Blätte: University Hospital of Ulm
Sabrina Skambraks: University Hospital of Ulm
Jan Krönke: University Hospital of Ulm
Florian H. Heidel: Friedrich-Schiller-University Medical Center
Tina M. Schnöder: Friedrich-Schiller-University Medical Center
Andrea Corbacioglu: University Hospital of Ulm
Verena I. Gaidzik: University Hospital of Ulm
Peter Paschka: University Hospital of Ulm
Veronica Teleanu: University Hospital of Ulm
Gudrun Göhring: Hannover Medical School
Felicitas Thol: Hannover Medical School
Michael Heuser: Hannover Medical School
Arnold Ganser: Hannover Medical School
Daniela Weber: University Hospital of Ulm
Eric Sträng: Ulm University
Hans A. Kestler: Ulm University
Hartmut Döhner: University Hospital of Ulm
Lars Bullinger: University Hospital of Ulm
Konstanze Döhner: University Hospital of Ulm

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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 (NPM1mut) AML, we assess mutation status of five recurrently mutated oncogenes in 129 paired NPM1mut samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1mut loss (n = 11). To better understand these NPM1mut loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1mut 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 NPM1mut are reflected by a high overlap of mutations between diagnosis and relapse. Our findings confirm that relapse often originates from persistent leukemic clones, though NPM1mut loss cases suggest a second “de novo” or treatment-associated AML (tAML) as alternative cause of relapse.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09745-2

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DOI: 10.1038/s41467-019-09745-2

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