The potential of venetoclax (ABT 199) in chronic lymphocytic leukemia
Venetoclax (VEN, ABT 199/GDC 0199) is an orally bioavailable BH3 mimetic that specifically inhibits the anti apoptotic B cell lymphoma/leukemia 2 (BCL2) protein. Although BCL2 overexpression is not genetically driven in chronic lymphocytic leukemia (CLL) it is nearly universal and represents a highly important and prevalent mechanism of apoptosis evasion, making it an attractive therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data regarding the effectiveness and safety of VEN. We further strive to contextualize VEN in the current CLL treatment landscape and discuss potential mechanisms of resistance.
Therapeutic advances in hematology