Conference Proceedings
Detection of Multiple Recurrent Novel BCL2 Mutations Co-Occurring with BCL2 Gly101Val in Patients with Chronic Lymphocytic Leukemia on Long Term Venetoclax
Piers Blombery, Ella Thompson, Nguyen Tamia, Xiangting Chen, Michelle McBean, Richard W Birkinshaw, Peter E Czabotar, Rachel Thijssen, Mary Ann Anderson, John F Seymour, David Alan Westerman, David CS Huang, Andrew W Roberts
BLOOD | AMER SOC HEMATOLOGY | Published : 2019
Abstract
The BCL2 Gly101Val mutation may be acquired in patients with chronic lymphocytic leukaemia (CLL) treated with venetoclax (VEN), leading to reduced drug binding affinity and secondary resistance. In the majority of patients, the Gly101Val mutation is subclonal within the CLL compartment consistent with the presence of alternative resistance mechanisms in CLL cells not harboring the Gly101Val mutation. To date, two Gly101Val mutated patients have been identified with co-existing candidate resistance mechanisms in Gly101Val non-mutated cells; one with BCL-XL over-expression (Blombery et al, Cancer Discov., 2019) and another with a second subclonal candidate BCL2 resistance mutation - Asp103Tyr ..
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