Selective HDAC6 inhibition perturbs autophagy and enhances integrated stress response-mediated immunogenic apoptosis in chronic myeloid leukemia - PubMed
5 hours ago
- #CML therapy
- #autophagy disruption
- #HDAC6 inhibition
- Selective HDAC6 inhibitor 7b reduces CML cell viability, sparing healthy cells, and is effective in vivo.
- Combining 7b with asciminib synergistically suppresses CML cell growth and triggers immunogenic apoptosis.
- 7b blocks autophagosome maturation, disrupting autophagy and activating the integrated stress response (ISR) with eIF2α phosphorylation and CHOP induction.
- ISR activation leads to mitochondrial apoptosis via MCL-1 suppression and PUMA/NOXA upregulation, dependent on BCL-xL and caspase cascades.
- The combination induces immunogenic cell death markers such as calreticulin exposure, ATP and HMGB1 release, and altered cytokine levels.