A02: Mitochondrial RNA modification-driven metabolic plasticity in leukemic stem cells and drug resistance

Project A02 will map and quantify m1G levels in mitochondrial- and nuclear-encoded tRNAs in healthy hematopoietic stem and progenitor cells and matched leukemia samples (diagnosis and relapse). Subsequently, the underlying molecular mechanisms of how mitochondrial and cytosolic mRNA translation rates are coordinated in normal and malignant hematopoietic cells will be identified. Inhibition of oncogenic pathways inducing mitochondrial RNA modifications will test whether metabolic plasticity can be blocked and leukemic cells can be re-sensitized to anti-leukemic drug treatment.