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Association details:
Evidence:
Evidence Level:
Resistant: D – Preclinical
New
Title:

Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia

Excerpt:
...in the biochemical and cellular assays, we found venetoclax to be less effective against the Gly101Val mutant, and this probably accounts for the reduced sensitivity of the cells to venetoclax....In the absence of venetoclax, the WT and Gly101Val-expressing cells grew at similar rates. However, in the presence of a sublethal dose of venetoclax, the latter outcompeted WT cells....Although our experimental data indicate that the Gly101Val mutation is sufficient to confer resistance to venetoclax and outgrowth of mutation-bearing clones in the presence of continuous venetoclax exposure in vitro and in patients, our data also indicate that other mechanisms for development of resistance are clinically important. 
DOI:
10.1158/2159-8290.CD-18-1119