Leveraging Increased Nucleoside Kinase Activity to Selectively Deplete Mitochondrial DNA (mtDNA), Impair Oxidative Phosphorylation, and Target AML Cells
Abstract:Mitochondrial DNA (mtDNA) replication requires adequate nucleotide pools from the mitochondria and cytoplasm to support DNA biosynthesis. Gene expression profiling of 542 AML patient samples (GSE13159) demonstrated that 55% of AML patients had upregulated mtDNA biosynthesis pathway expression compared to 73 normal hematopoietic cells (mononuclear cells isolated from peripheral blood and bone marrow). We also identified upregulation of pathways which support mitochondrial nucleotide pools, which include mitocho… Show more
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