Biomedical Sciences ETDs

Publication Date

Fall 12-11-2022

Abstract

Acute Myeloid Leukemia (AML) patients respond favorably to induction chemotherapy, however, long-term outcomes remain poor due to a high rate of chemoresistance and bone marrow minimal residual disease. To improve long-term patient outcomes, it’s critical to identify regulators of chemotherapy resistance in AML and develop therapies that are directed towards bone marrow resident AML cells. In Chapter 2, we uncover the impact of CD82 expression in AML response to chemotherapeutic treatment and the contribution of Protein Kinase C α (PKCα) and β1 integrin signaling in promoting p38 MAPK activation to support CD82-mediated AML cell survival. In Chapter 3, we demonstrate that CD82 regulates AML cell quiescence in the bone marrow niche through the activation of TGF-β-SMAD2/3 signaling and promoting crosstalk with β1 integrin. Collectively, the studies described in this dissertation uncover novel mechanisms of AML chemoresistance and dormancy and identify potential clinical targets to improve long-term patient outcomes.

Keywords

AML, BSGP, CD82, Tetraspanin, Resistance, MRD

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Dr. Jennifer Gillette

Second Committee Member

Dr. Angela Wandinger-Ness

Third Committee Member

Dr. Diane Lidke

Fourth Committee Member

Dr. Scott Ness

Available for download on Monday, December 12, 2022

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