Mitochondrial Genome Alterations Seen as a Risk Factor for Pediatric Acute Myeloid Leukemia

Alterations in mitochondrial DNA (mtDNA) are associated with the risk for pediatric acute myeloid leukemia (AML), according to a study titled “Clinicopathological Implications of Mitochondrial Genome Alterations in Pediatric Acute Myeloid Leukemia” and published in the journal Annals of Laboratory Medicine.

Mitochondria are key organelles within cells that are responsible for generating the energy cells need to work. They are also a unique organelle because they have their own independent genome. Recently, it was suggested that mutations in the mtDNA are associated with tumorigenesis, notably due to an increased production of damaging reactive oxygen species (ROS), which enhances the metastatic potential of tumor cells. Disease can also arise by variations in mtDNA copy numbers, where the decrease or depletion of mtDNA copy number — literally, the number of copies — has been associated with human hepatocellular carcinoma, infantile neurogenetic disorders, breast cancer, renal cell carcinoma, and osteosarcoma in Chinese patients. Elevated mtDNA copy numbers, likewise, associate with colorectal cancer tissues and increased risk of non-Hodgkin lymphoma.

A team of researchers analyzed, for the first time, mtDNA aberrations in pediatric AML patients and their clinical outcomes. To this end, researchers enrolled, at the time of diagnosis, 55 pediatric AML patients and 55 healthy controls (matched for age and gender) from the Environmental Health Center for Childhood Leukemia and Cancer Cohort of Korea between February 2004 and February 2012. They determined the mtDNA copy number of patients and controls, and mtDNA large deletions, by sequencing bone marrow mononuclear cells. Moreover, researchers examined alterations in mitochondrial mass, mitochondrial membrane potential, and intracellular ROS in both groups.

The team observed that, when compared to controls, pediatric AML cells had a two-fold increase in mtDNA copy numbers. Most importantly, researchers found a close relationship between mtDNA copies and the risk of pediatric AML. Concomitantly, AML patients exhibited elevated levels of intracellular ROS, mitochondrial mass, and mitochondrial membrane potentials. Furthermore, the frequency of the mtDNA large deletion (of 4,977 base pairs) was also significantly higher in pediatric AML cells. Despite observing an association between elevated mtDNA deletions and shorter overall survival, this association did not reach statistical significance.

In conclusion, researchers reported for the first time an association between mitochondrial genome alterations and the risk for pediatric AML.