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ASH 2020 | ETNK1 mutations precede mitochondrial dysfunction in atypical CML
Diletta Fontana, PhD, Department of Medicine and Surgery, University of Milan – Bicocca, Monza, MB, Italy, discusses the results of a study investigating the role of ETNK1 kinase mutations in atypical chronic myeloid leukemia (ACML). ETNK1 mutations are responsible for increased mitochondrial activity, ROS production and subsequently oxidative DNA damage. The phenotype was found to be dependent on a decreased concentration of phosphoethanolamine, a product of an ETNK1 catalysis reaction. Further analysis demonstrated phosphoethanolamine is a competitive inhibitor of succinate dehydrogenase in the mitochondrial complex II, whereby a decrease in ETNK1 kinase activity directly increases mitochondrial activity. Promising in vitro assays suggest the mechanism of increased mitochondrial activity and therefore ROS production and DNA damage can be blocked by supplementation with phosphoethanolamine. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
