Targeting SMC3 deacetylation synergizes with XPO1 inhibition to reprogram the epigenetic landscape and suppress NPM1-mutated acute myeloid leukemia - PubMed
3 hours ago
- #targeted therapy
- #epigenetics
- #acute myeloid leukemia
- ESCO2 deficiency promotes NPM1-mutated AML progression by destabilizing cohesin and NuRD complex on chromatin, enhancing leukemia self-renewal gene expression.
- HDAC8 inhibition restores SMC3 binding, induces differentiation and apoptosis, and when combined with XPO1 inhibition, reverses aberrant epigenetic landscapes.
- The combined targeting effectively suppresses NPM1-mutated AML cells in vitro and in vivo, offering a potential therapeutic strategy for this AML subtype.