Abstract
Mitochondrial DNA (mtDNA) copy number alterations occur in acute myeloid leukemia (AML). We evaluated regulation and biological significance of mtDNA copy number in pediatric AML patients (n = 123) by qRT-PCR, and in-vitro studies. MtDNA copy number was significantly higher (p < 0.001) and an independent predictor of aggressive disease (p = 0.006), lower event free survival (p = 0.033), and overall survival (p = 0.007). Expression of TFAM, POLG, POLRMT, MYC and ND3 were significantly upregulated. In cell lines, PGC1A inhibition decreased mtDNA copy number while MYC inhibition had no effect. PGC1A may contribute to enhanced mtDNA copy number, which predicts disease aggressiveness and inferior survival outcome.
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