BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia - PubMed
6 hours ago
- #Translation Elongation
- #Ribotoxic Stress Response
- #Chronic Myeloid Leukemia
- BCR::ABL1 inhibitors in CML cause ribosome collisions and activate the ribotoxic stress response (RSR).
- ZAK expression increases with CML progression; it promotes AKT activity but is paradoxically needed for inhibitor-induced apoptosis.
- Inhibitors slow translation via mTOR-EEF2K and EEF2 phosphorylation, leading to collided ribosomes that trigger ZAK-p38 activation and apoptosis.
- Translation flux modulation affects BCR::ABL1 inhibitor efficacy, showing RSR as a therapeutic target in CML.