Inflammatory Bowel Disease-induced Inflammation Augments Clonal Hematopoiesis of Indeterminate Potential through Ref-1 - PubMed
3 hours ago
- #CHIP
- #IBD
- #Inflammation
- Clonal hematopoiesis of indeterminate potential (CHIP) is linked to age-related somatic mutations in hematopoietic stem and progenitor cells (HSC/Ps).
- CHIP is associated with increased risks of myeloid malignancies, inflammation-related diseases, and higher mortality.
- Inflammatory Bowel Disease (IBD) patients with CHIP show higher incidence rates, especially females with DNMT3A mutations.
- For Crohn's disease, DNMT3A mutations increase incidence by 1.81-fold in females, rising to 2.09 for large clones.
- For ulcerative colitis, TET2 large clones are significantly associated, particularly in individuals under 45.
- Mouse models show worse IBD pathophysiology in HSC/Ps with Dnmt3a mutation due to heightened APE1 expression.
- Treatment with APE1/Ref-1 inhibitor APX3330 ameliorates CHIP-IBD driven by Dnmt3a mutation.