Detection and Targeting of Enzymatic Base Editing Deregulation in Leukemia Stem Cells
Catriona Jamieson
PhD, MDUniversity of California, San Diego
Project Term: July 1, 2020 - June 30, 2023
Dr. Jamieson is examining the role of two enzymes (APOBEC3 and ADAR1) known to mutate DNA and RNA, and their role in acute myeloid leukemia (AML) and disease relapse, particularly in elderly patients.
Progression of acute myeloid leukemia (AML) is driven by leukemic stem cells (LSCs), and blocking the growth of LSCs is a central strategy in preventing AML recurrence. Dr. Catriona Jamieson’s project is focused on certain alterations of DNA and RNA (called “base editing”) that promote the proliferation of LSCs. Her goal is to understand how base editing supports LSC growth and to develop therapeutic approaches to inhibit this process. One aspect of the study will be to determine whether genetic manipulation or pharmacological agents can block activation of a particular enzyme, ADR1, required for base editing in LSCs. A second project aim will be to investigate approaches for inhibiting a different base-editing enzyme (called APOBEC3C). The third aim will investigate how altered forms of a key signaling component, STAT3, contribute to LSC proliferation and test the potential of a specific drug to block this AML-promoting activity. Each of these approaches can lead to the development of novel therapeutic agents that inhibit or kill AML cells in recurring disease.
This Discovery award is sponsored through a partnership between LLS, the Mark Foundation for Cancer Research and The Paul G. Allen Frontiers Group.