Abstract:Background: Resistance to chemotherapy-induced apoptotic death is a major mechanism responsible for the failure of AML therapies. Levels of anti-apoptotic proteins BCL2 and MCL1 are increased in relapsed AML samples. Venetoclax, a BH3 mimetic that binds to BCL-2, was recently granted accelerated approval for use in AML in combination with cytotoxic chemotherapy. However, MCL-1 and BCL-XL are known pathways of resistance to BCL-2 directed therapy. AMG-176 is a first-in-class MCL-1 specific inhibitor that induce… Show more
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