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NSUN2-FOSB reciprocity facilitates leukemogenesis in an m5C-dependent manner by increasing BCL2L1 expression - PubMed

a day ago
  • #AML
  • #RNA methylation
  • #leukemogenesis
  • NSUN2 is upregulated in AML patient samples compared to normal hematopoietic cells.
  • NSUN2 knockdown impairs AML cell proliferation, induces apoptosis, and reduces colony formation.
  • Genetic ablation of NSUN2 in a murine AML model impairs leukemia stem cell self-renewal and prolongs survival.
  • NSUN2's effects on leukemogenesis are dependent on its catalytic activity for m5C RNA modification.
  • NSUN2 stabilizes FOSB mRNA via m5C modification, leading to increased FOSB expression.
  • FOSB transcriptionally activates NSUN2, creating a feedforward regulatory loop.
  • FOSB promotes BCL2L1 expression by binding to its promoter, enhancing anti-apoptotic effects.
  • The NSUN2-FOSB-BCL2L1 axis is identified as a key driver of AML leukemogenesis in an m5C-dependent manner.