Childhood Cancer

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Immunogenicity of Acute Myeloid Leukemia after Chemotherapy and PARP inhibition

Institution: 
Dartmouth-Hitchcock Clinic
Researcher(s): 
Isabelle Aldrige
Grant Type: 
POST Program Grants
Year Awarded: 
2023
Type of Childhood Cancer: 
Leukemia
Project Description: 

Mentor Name: Bonnie Lau

Acute myeloid leukemia (AML) in children has poor prognosis. Even after successfully getting patients into remission, 40% of the patients end up having relapse of disease which is often deadly. These "persister" leukemia cells that cause deadly AML relapse need to be better characterized so we can target these cells more directly to prevent relapse. We have preliminary data that the DNA damage accumulated by the AML cells after standard chemotherapy treatment can be enhanced with a newer DNA damaging drug called PARP inhibitor. AML cells with increased DNA damage are expressing a checkpoint protein on the cell surface, which can be targeted with immune checkpoint inhibitor immunotherapy. This project aims to profile the expression of immune checkpoints and genetic markers of being more "immunogenic" on these persister AML cells by using flow cytometry and RNA sequencing. If these persister AML cells are more immunogenic, then we would hypothesize that these cells can be treated with immunotherapies in order to prevent deadly AML relapse.