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IN VIVO ACTIVITY OF THE SECOND-GENERATION PROTEASOME INHIBITOR IXAZOMIB AGAINST PEDIATRIC T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA XENOGRAFTS.
Experimental Hematology 2024 Februrary 5
The overall survival rate of patients with T-cell acute lymphoblastic leukemia (T-ALL) is now 90%, although patients with relapsed T-ALL face poor prognosis. The ubiquitin-proteasome system maintains normal protein homeostasis, and aberrations in this pathway are associated with T-ALL. Here we demonstrate the in vitro and in vivo activity of ixazomib, a second-generation orally available, reversible, and selective proteasome inhibitor against pediatric T-ALL cell lines and patient-derived xenografts (PDXs) grown orthotopically in immune-deficient NSG mice. Ixazomib was highly potent in vitro, with IC50 values in the low nanomolar range. As a monotherapy, ixazomib significantly extended mouse event-free survival of five out of eight T-ALL PDXs in vivo.
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