Drs Richard Birkinshaw, Mary Ann Anderson & Rachel Thijssen - Structural Biology & BCBC divisions

Drs Richard Birkinshaw, Mary Ann Anderson & Rachel Thijssen - Structural Biology & BCBC divisions

Location: 
Davis Auditorium
Start Time: 
Wed, 27/03/2019 - 1:00pm
End Time: 
Wed, 27/03/2019 - 2:00pm

Venetoclax Resistance - The G101V mutation story

Wednesday seminar​

For many patients especially those with chronic lymphocytic leukemia (CLL) venetoclax has proved a lifesaving drug prolonging both the duration and quality of life through restoration of the malignant cells ability to undergo apoptotic cell death.

Unfortunately by two years on venetoclax approximately 50% of relapsed and refractory CLL patients will have developed clinical resistance with the recrudescence of disease manifestations. While the reasons for venetoclax resistance are likely to be heterogeneous in different patients and also between different disease types, our work is beginning to provide insights into contributing factors for the development of venetoclax resistance.

One of these factors contributing to CLL resistance to venetoclax is the G101V mutation that we have demonstrated is present at the time of CLL progression among some patients with venetoclax resistance but not present at study entry. Our subsequent work has demonstrated reduced affinity for venetoclax binding among cells harboring this mutation with a consequent reduction in in vitro sensitivity to the drug.