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

Nature Communications
Carmen D HerlingMartin Peifer

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.

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Datasets Mentioned

BETA
PRJEB24344

Methods Mentioned

BETA
methylation profiling
exome-sequencing
PCR
exome sequencing
flow cytometry
biopsy
electrophoresis
transfection
FCS
fluorescence-activated cell sorting

Clinical Trials Mentioned

NCT01889186
NCT02401503

Software Mentioned

IDAT
QuantaSoft
R
LI
Pars
BWA mem aligner
COR
PHYLIP package
RnBeads
Bioconductor

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