Effective targeting of NAMPT in patient-derived xenograft models of high-risk pediatric acute lymphoblastic leukemia.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Cell Survival
/ drug effects
Cytokines
/ antagonists & inhibitors
Enzyme Inhibitors
/ pharmacology
Humans
Mice
Nicotinamide Phosphoribosyltransferase
/ antagonists & inhibitors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Xenograft Model Antitumor Assays
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
30
05
2019
accepted:
05
12
2019
revised:
21
11
2019
pubmed:
19
12
2019
medline:
8
10
2020
entrez:
19
12
2019
Statut:
ppublish
Résumé
The prognosis for children diagnosed with high-risk acute lymphoblastic leukemia (ALL) remains suboptimal, and more potent and less toxic treatments are urgently needed. We investigated the efficacy of a novel nicotinamide phosphoribosyltransferase inhibitor, OT-82, against a panel of patient-derived xenografts (PDXs) established from high-risk and poor outcome pediatric ALL cases. OT-82 was well-tolerated and demonstrated impressive single agent in vivo efficacy, achieving significant leukemia growth delay in 95% (20/21) and disease regression in 86% (18/21) of PDXs. In addition, OT-82 enhanced the efficacy of the established drugs cytarabine and dasatinib and, as a single agent, showed similar efficacy as an induction-type regimen combining three drugs used to treat pediatric ALL. OT-82 exerted its antileukemic action by depleting NAD
Identifiants
pubmed: 31848452
doi: 10.1038/s41375-019-0683-6
pii: 10.1038/s41375-019-0683-6
pmc: PMC9110273
mid: NIHMS1801536
doi:
Substances chimiques
Antineoplastic Agents
0
Cytokines
0
Enzyme Inhibitors
0
Nicotinamide Phosphoribosyltransferase
EC 2.4.2.12
nicotinamide phosphoribosyltransferase, human
EC 2.4.2.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1524-1539Subventions
Organisme : NCI NIH HHS
ID : U01 CA199000
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199222
Pays : United States
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