Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia

Carmen D. Herling, Nima Abedpour, Jonathan Weiss, Anna Schmitt, Ron Daniel Jachimowicz, Olaf Merkel, Maria Cartolano, Sebastian Oberbeck, Petra Mayer, Valeska Berg, Daniel Thomalla, Nadine Kutsch, Marius Stiefelhagen, Paula Cramer, Clemens-Martin Wendtner, Thorsten Persigehl, Andreas Saleh, Janine Altmüller, Peter Nürnberg, Christian Pallasch, Viktor Achter, Ulrich Lang, Barbara Eichhorst, Roberta Castiglione, Stephan C. Schäfer, Reinhard Büttner, Karl-Anton Kreuzer, Hans Christian Reinhardt, Michael Hallek, Lukas P. Frenzel and Martin Peifer ()
Additional contact information
Carmen D. Herling: University of Cologne
Nima Abedpour: University of Cologne
Jonathan Weiss: University of Cologne
Anna Schmitt: University of Cologne
Ron Daniel Jachimowicz: University of Cologne
Olaf Merkel: University of Cologne
Maria Cartolano: University of Cologne
Sebastian Oberbeck: University of Cologne
Petra Mayer: University of Cologne
Valeska Berg: University of Cologne
Daniel Thomalla: University of Cologne
Nadine Kutsch: University of Cologne
Marius Stiefelhagen: University of Cologne
Paula Cramer: University of Cologne
Clemens-Martin Wendtner: Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing
Thorsten Persigehl: Cologne University Hospital
Andreas Saleh: Städtisches Klinikum München Schwabing
Janine Altmüller: University of Cologne
Peter Nürnberg: University of Cologne
Christian Pallasch: University of Cologne
Viktor Achter: University of Cologne
Ulrich Lang: University of Cologne
Barbara Eichhorst: University of Cologne
Roberta Castiglione: University of Cologne
Stephan C. Schäfer: University of Cologne
Reinhard Büttner: University of Cologne
Karl-Anton Kreuzer: University of Cologne
Hans Christian Reinhardt: University of Cologne
Michael Hallek: University of Cologne
Lukas P. Frenzel: University of Cologne
Martin Peifer: University of Cologne

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03170-7

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