Understanding and overcoming therapy resistance remains one of the central challenges in cancer research. A publication by Cornelius Pauli (A02 project) in Blood contributes important insights into this question.
Therapy resistance in acute myeloid leukemia (AML) remains a major clinical challenge. In this study, the authors identify the tRNA methyltransferase TRMT5, which catalyzes the m¹G37 tRNA modification as a key regulator of mitochondrial translation and oxidative phosphorylation. This enables leukemia cells to sustain mitochondrial function and adapt under therapeutic pressure.
The study demonstrates that drug-tolerant leukemia cells upregulate oxidative phosphorylation as an adaptive response to therapy. In contrast, TRMT5 depletion impairs this metabolic adaption, leading to mitochondrial dysfunction and increased treatment sensitivity. These findings uncover a previously unrecognized mitochondrial vulnerability and highlight metabolic plasticity as a critical driver of therapy resistance in leukemia.
Furthermore, targeting TRMT5 was found to enhance therapeutic efficacy, suggesting potential combinatorial strategies with established treatments.
Overall, this work represents a significant contribution from the A02 project and highlights the broader research focus of CRC1709 on identifying novel therapeutic strategies in cancer.
We warmly congratulate Cornelius Pauli and his team on this achievement.
