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

Nat Commun 2018 02 20;9(1):727. Epub 2018 Feb 20.

Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.

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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http://dx.doi.org/10.1038/s41467-018-03170-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820258PMC
February 2018
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