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Free keywords:
Bridged Bicyclo Compounds, Heterocyclic/*therapeutic use
Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18/genetics/metabolism
*Drug Resistance, Neoplasm
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/genetics/metabolism
Male
Mutation
Neoplasm Proteins/genetics/metabolism
Sulfonamides/*therapeutic use
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.
