Ribosomal protein mutation increases BCL-2 in T-ALL subgroup
In pediatric T-ALL targeted treatments aimed at specific genetic subgroups may help improve survival rates and reduce long-term toxicity. Eight percent of pediatric T-ALL patients carry the R98S mutation in ribosomal protein L10 (RPL R98S). This mutation leads to enhanced β-oxidation in peroxisomes, resulting in increased levels of reactive oxygen species (ROS), mitochondrial dysfunction and hypoproliferation. High ROS levels often result in apoptosis. However, RPL10 R98S mutant ribosomes show a selective preference for IRES-dependent translation of the anti-apoptotic protein BCL-2, allowing for cell survival, as was presented by Dr Kim Kampen (KU Leuven, Belgium). In xenografted mouse models RPL10 R98S positive T-ALL samples were highly sensitive to the BCL-2 inhibitor ABT-199.