Bortezomib Restores Venetoclax Sensitivity in Acute Myeloid Leukemia Cell Lines with Intrinsic and Acquired Resistance - PubMed
5 hours ago
- #Acute Myeloid Leukemia
- #Bortezomib
- #Venetoclax Resistance
- Bortezomib, a proteasome inhibitor, synergizes with venetoclax to induce apoptosis in AML cell lines, including those with RAS or TP53 mutations.
- Mechanistically, bortezomib upregulates pro-apoptotic proteins like NOXA, BIM, and PUMA, which counteract MCL1 and promote apoptosis, with NOXA playing a key role.
- The combination of bortezomib and venetoclax resensitizes AML cell lines with both intrinsic and acquired resistance to venetoclax-based regimens.
- In vivo studies show that bortezomib-venetoclax combination significantly prolongs survival in mice with venetoclax-resistant AML cell lines harboring BAX mutations.
- The findings support the venetoclax-bortezomib combination as a potential strategy to overcome venetoclax resistance in certain AML subsets.