In vivo activity of the second-generation proteasome inhibitor ixazomib against pediatric T-cell acute lymphoblastic leukemia xenografts.
Exp Hematol
; 132: 104176, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38320689
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Boron Compounds
/
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
/
Glycine
Limits:
Animals
/
Child
/
Humans
Language:
En
Journal:
Exp Hematol
Year:
2024
Document type:
Article