Details

Autor(en) / Beteiligte

• Greif, Philipp A
• Hartmann, Luise
• Vosberg, Sebastian
• Stief, Sophie M
• Mattes, Raphael
• Hellmann, Ines
• Metzeler, Klaus H
• Herold, Tobias
• Bamopoulos, Stefanos A
• Kerbs, Paul
• Jurinovic, Vindi
• Schumacher, Daniela
• Pastore, Friederike
• Bräundl, Kathrin
• Zellmeier, Evelyn
• Ksienzyk, Bianka
• Konstandin, Nikola P
• Schneider, Stephanie
• Graf, Alexander
• Krebs, Stefan
• Blum, Helmut
• Neumann, Martin
• Baldus, Claudia D
• Bohlander, Stefan K
• Wolf, Stephan
• Görlich, Dennis
• Berdel, Wolfgang E
• Wörmann, Bernhard J
• Hiddemann, Wolfgang
• Spiekermann, Karsten

Titel

Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and Relapse: An Exome Sequencing Study of 50 Patients

Ist Teil von

• Clinical cancer research, 2018-04, Vol.24 (7), p.1716-1726

Ort / Verlag

United States: American Association for Cancer Research Inc

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• To study mechanisms of therapy resistance and disease progression, we analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML) based on somatic alterations. We performed exome sequencing of matched diagnosis, remission, and relapse samples from 50 CN-AML patients treated with intensive chemotherapy. Mutation patterns were correlated with clinical parameters. Evolutionary patterns correlated with clinical outcome. Gain of mutations was associated with late relapse. Alterations of epigenetic regulators were frequently gained at relapse with recurring alterations of constituting a mechanism of cytarabine resistance. Low expression correlated with adverse clinical outcome, particularly in male patients. At complete remission, persistent mutations representing preleukemic lesions were observed in 48% of patients. The persistence of mutations correlated with shorter time to relapse. Chemotherapy resistance might be acquired through gain of mutations. Insights into the evolution during therapy and disease progression lay the foundation for tailored approaches to treat or prevent relapse of CN-AML. .