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Mutant ribosomal protein RPS15 drives B cell malignancy through oxidative stress and genomic instability - PubMed

7 hours ago
  • #Oxidative stress
  • #Ribosomal mutation
  • #B-cell leukemia
  • Mutant ribosomal protein RPS15 (S138F) drives B cell malignancy.
  • Mutation causes ribosome biogenesis defects, altered translation, oxidative stress, and DNA damage.
  • Induces p53-dependent response leading to initial hypo-proliferation.
  • Aged mice with mutation develop B-cell leukemia (37% penetrance) with increased Myc activity.
  • Translational rewiring and genomic instability enable acquisition of additional mutations (e.g., TP53 deletion).
  • Mutation overcomes anti-cancer barriers to trigger tumorigenesis.