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

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-inhibit...

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Detalles Bibliográficos
Autores principales: 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, Altmüller, Janine, Nürnberg, Peter, Pallasch, Christian, Achter, Viktor, Lang, Ulrich, Eichhorst, Barbara, Castiglione, Roberta, Schäfer, Stephan C., Büttner, Reinhard, Kreuzer, Karl-Anton, Reinhardt, Hans Christian, Hallek, Michael, Frenzel, Lukas P., Peifer, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820258/
https://www.ncbi.nlm.nih.gov/pubmed/29463802
http://dx.doi.org/10.1038/s41467-018-03170-7
Descripción
Sumario: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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