Abstract

Deciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.

Details

Title
Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia
Author
Herling, Carmen D 1 ; Abedpour, Nima 2 ; Weiss, Jonathan 1 ; Schmitt, Anna 3 ; Jachimowicz, Ron Daniel 3 ; Merkel, Olaf 4 ; Cartolano, Maria 2 ; Oberbeck, Sebastian 5 ; Mayer, Petra 5 ; Berg, Valeska 4 ; Thomalla, Daniel 4 ; Kutsch, Nadine 1 ; Stiefelhagen, Marius 1 ; Cramer, Paula 1 ; Clemens-Martin Wendtner 6 ; Persigehl, Thorsten 7 ; Saleh, Andreas 8 ; Altmüller, Janine 9 ; Nürnberg, Peter 10 ; Pallasch, Christian 3 ; Achter, Viktor 11 ; Lang, Ulrich 12 ; Eichhorst, Barbara 1 ; Castiglione, Roberta 13 ; Schäfer, Stephan C 13 ; Büttner, Reinhard 13 ; Karl-Anton Kreuzer 1 ; Reinhardt, Hans Christian 3 ; Hallek, Michael 3 ; Frenzel, Lukas P 4 ; Peifer, Martin 2   VIAFID ORCID Logo 

 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany 
 Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany 
 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany 
 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany 
 Department of Internal Medicine I, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Laboratory of Lymphocyte Signaling and Oncoproteom, University of Cologne, 50931 Cologne, Germany 
 Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, 80804 Munich, Germany 
 Department of Radiology, Cologne University Hospital, 50937 Cologne, Germany 
 Department of Diagnostic and Interventional Radiology and Pediatric Radiology, Städtisches Klinikum München Schwabing, 80804 Munich, Germany 
 Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany 
10  Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany; Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany 
11  Computing Center, University of Cologne, 50931 Cologne, Germany 
12  Computing Center, University of Cologne, 50931 Cologne, Germany; Department of Informatics, University of Cologne, 50931 Cologne, Germany 
13  Department of Pathology, University of Cologne, Cologne, Germany 
Pages
1-8
Publication year
2018
Publication date
Feb 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2006814055
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.