Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 29463802.
- Also identified by DOI 10.1038/s41467-018-03170-7 and PMC identifier 5820258.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Bridged Bicyclo Compounds, Heterocyclic
- Drug Resistance, Neoplasm
- Leukemia, Lymphocytic, Chronic, B-Cell
- Sulfonamides