Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia
- Herling, Carmen D.
- Abedpour, Nima
- Weiss, Jonathan
- Schmitt, Anna
- Jachimowicz, Ron Daniel
- Merkel, Olaf
- Cartolano, Maria
- Oberbeck, Sebastian
- Mayer, Petra
- Berg, Valeska
- Thomalla, Daniel
- Kutsch, Nadine
- Stiefelhagen, Marius
- Cramer, Paula
- Wendtner, Clemens-Martin
- Persigehl, Thorsten
- Saleh, Andreas
- Altmueller, Janine
- Nuernberg, Peter
- Pallasch, Christian
- Achter, Viktor
- Lang, Ulrich
- Eichhorst, Barbara
- Castiglione, Roberta
- Schaefer, Stephan C.
- Buettner, Reinhard
- Kreuzer, Karl-Anton
- Reinhardt, Hans Christian
- Hallek, Michael
- Frenzel, Lukas P.
- Peifer, Martin
Publication date
January 2018
DOI Publisher
Springer Science and Business Media LLCAbstract
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
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