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Randall, Joanna; Evans, Kathryn; Watts, Ben; Kosasih, Hansen J.; Smith, Christopher M.; Earley, Eric J.; Erickson, Stephen W.; Jocoy, Emily L.; Bult, Carol J.; Teicher, Beverly A.; de Bock, Charles E.; Smith, Malcolm A.; Lock, Richard B.
Experimental hematology, April 2024, 2024-Apr, 2024-04-00, 20240401, Letnik: 132Journal Article
•Ixazomib is an orally available, reversible selective proteasome inhibitor•Ixazomib elicited IC50 values in the low nanomolar range in T-ALL cell models in vitro•Ixazomib treatment of PDX models in vivo resulted in a modest increase in survival 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 immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJAusb (NSG) mice. Ixazomib was highly potent in vitro, with half-maximal inhibitory concentration (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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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