Determining the Effect of Mitochondrial Respiration-Targeted Drugs on Leukemia Stem Cells in a Mouse Model of Acute Myeloid Leukemia

Mia Corradi

Document Type

Article

Publication Date

8-9-2024

Keywords

JMG

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Acute myeloid leukemia (AML) is a blood cancer that results in an abundance of abnormal blood cells. Within AML, a population of cells termed leukemia stem cells (LSCs) propagate malignancy and are largely resistant to chemotherapy, highlighting the need for a better understanding of these cells’ biology to improve treatment of AML. LSCs are known to rely on oxidative phosphorylation (OXPHOS), making mitochondrial activity a potential target for AML therapy that is also effective at depleting LSCs. By utilizing a Dmnt3aR878H/+ Npm1cA/+ mouse AML model developed by the Trowbridge lab, we aim to determine if drugs that target mitochondrial respiration can suppress the growth of AML LSCs. Therefore, we hypothesize that three mitochondrially-targeted molecules that reduce OXPHOS (MitoQ, metformin, and venetoclax) will reduce the growth of LSCs in a mouse model of Dnmt3aR878H/+ Npm1cA/+ AML. To test this, spleen and/or bone marrow samples were attained from Dnmt3aR878H/+ Npm1cA/+ non-disease and AML mice to determine in vitro cell viability after drug treatment. Our preliminary data suggests mitochondrial respiration-targeted drugs decrease cell viability in the context of AML but are less effective in the non-disease state. Further experimentation is necessary to understand the true impacts of these drugs to treat AML.

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