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Wayne State University Dissertations

Bcl-2

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Strategies To Enhance The Anti-Leukemic Activity Of Venetoclax (Abt-199) In Aml Through Targeting Of Mcl-1, Daniel Luedtke Jan 2019

Strategies To Enhance The Anti-Leukemic Activity Of Venetoclax (Abt-199) In Aml Through Targeting Of Mcl-1, Daniel Luedtke

Wayne State University Dissertations

Acute Myeloid Leukemia (AML) is a frustratingly difficult to treat disease (67% 5 year survival for children and 24% for adults). The standard of care, similar to outcomes, has seen few improvements over the last several decades. The Bcl-2 family, which controls cell survival and apoptosis, is dysregulated in AML. Bcl-2, which is overexpressed in AML and associated with chemoresistance, is a promising therapeutic target. The now FDA approved venetoclax (ABT-199) is a BH3 mimetic that is able to bind to anti-apoptotic Bcl-2 and prevent it from sequestering pro-apoptotic Bim. While overall response rates are promising, our lab and others …