FLT3-SYK inhibitor and Ixazomib combination impact HOXA and oxidative stress control by β-catenin, SQSTM1 and NRF2 in AML - PubMed
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- #AML
- #FLT3-SYK inhibitor
- #proteasome inhibition
- Combination of FLT3-SYK inhibitor (TAK-659) and proteasome inhibitor (Ixazomib) shows strong synergy in AML treatment.
- The therapy impacts HOXA genes and oxidative stress control via β-catenin, SQSTM1, and NRF2 pathways.
- Proteasome inhibition induces β-catenin ubiquitination and nuclear export, triggering stress signaling and apoptosis in FLT3ITD mutant AML.
- In mouse models, the combination therapy reduced leukemic burden and restored normal hematopoiesis.
- Clinical trial (NCT04079738) demonstrated rapid leukemic clearance and durable responses in refractory AML patients.
- The findings highlight a targetable axis linking FLT3/SYK/β-catenin to stress adaptation in high-risk AML.