Language
English
Publication Date
1-1-2025
Journal
PLoS One
DOI
10.1371/journal.pone.0324443
PMID
40526635
PMCID
PMC12173385
PubMedCentral® Posted Date
6-17-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Novel agents targeting upregulated signaling pathways are needed to improve outcomes in T-cell acute lymphoblastic leukemia (T-ALL), since conventional cytotoxic chemotherapy regimens have reached the limits of tolerability. We identified upregulated, targetable signaling pathways common to both human T-ALL samples and a KrasLSL-G12D/+.Mb1Cre/+ murine model of T-ALL. We found the NAMPT inhibitor FK866 had the greatest cytotoxicity of a panel of small molecule inhibitors tested in human and mouse T-ALL cell lines, and in patient derived xenograft (PDX)-expanded T-ALL patient samples. We subsequently tested FK866 in vivo in PDX mouse models of T-ALL, and found that it significantly reduced the peripheral blood disease burden and prolonged the survival of leukemic mice (median survival of 60.5 vs 21 days, p = 0.0007). This screen for targetable pathways in T-ALL generated in vitro and in vivo preclinical data supporting NAMPT inhibition as a promising strategy for the treatment of T-ALL.
Keywords
Nicotinamide Phosphoribosyltransferase, Animals, Humans, Mice, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Piperidines, Cytokines, Acrylamides, Cell Line, Tumor, Xenograft Model Antitumor Assays, Signal Transduction
Published Open-Access
yes
Recommended Citation
Vrana, Chelsea; Zhang, Matthew; Rochette, Max; et al., "Efficacy of Nampt Inhibition in T-Cell Acute Lymphoblastic Leukemia" (2025). Faculty, Staff and Students Publications. 6265.
https://digitalcommons.library.tmc.edu/baylor_docs/6265