Enhancing tyrosine kinase inhibitor sensitivity by restoring IKAROS activity on GLUT1 expression and glycolysis in Philadelphia chromosome-positive acute lymphoblastic leukemia - PubMed
4 days ago
- #TKIs
- #leukemia
- #glycolysis
- Ph+ ALL patients often show reduced sensitivity to tyrosine kinase inhibitors (TKIs).
- IKZF1 deletions and CK2-mediated hyperphosphorylation of IKAROS contribute to TKI resistance in Ph+ ALL.
- Combining TKIs (imatinib or ponatinib) with CK2 inhibitor CX-4945 improves survival and reduces tumor burden in Ph+ ALL PDX models.
- GLUT1 overexpression and enhanced glycolysis are linked to TKI resistance in Ph+ ALL.
- Restoring IKAROS activity represses GLUT1 expression and suppresses glycolysis, enhancing TKI sensitivity.
- The study proposes a novel therapeutic strategy to overcome TKI resistance in Ph+ ALL by targeting glycolysis.