Oncology Commons^™

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 …

Identifying Mechanisms Of Resistance And Potential Therapeutic Targets For Pediatric Acute Myeloid Leukemia, John Timothy Caldwell

Wayne State University Dissertations

Acute myeloid leukemia (AML) is a potentially devastating disease that can affect people of all ages. While there are certain patient groups that typically have favorable outcomes, in the pediatric population, overall survival (OS) is approximately 70%, leaving much progress to be made. Children with Down syndrome (DS) have a substantially elevated risk for developing AML, especially of the megakaryocytic phenotype (AMKL).

Patients with DS AMKL almost universally harbor a mutation in the gene encoding the GATA1 transcription factor, resulting in the translation of a short-form protein GATA1s, which has been shown to contribute to chemotherapy sensitivity. In contrast, in …