Identification of small molecules that mitigate vincristine-induced neurotoxicity while sensitizing leukemia cells to vincristine.
Adolescent
Animals
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Cells, Cultured
Child
Drug Resistance, Neoplasm
/ genetics
Female
Gene Expression Regulation, Leukemic
Gene Knockdown Techniques
Humans
Induced Pluripotent Stem Cells
Male
Mice
Neurons
Peripheral Nervous System Diseases
/ chemically induced
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Primary Cell Culture
Ribonucleoproteins, Small Nuclear
/ antagonists & inhibitors
Vincristine
/ adverse effects
Xenograft Model Antitumor Assays
Young Adult
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
11
02
2021
received:
12
01
2021
accepted:
17
02
2021
pubmed:
21
3
2021
medline:
15
2
2022
entrez:
20
3
2021
Statut:
ppublish
Résumé
Vincristine (VCR) is one of the most widely prescribed medications for treating solid tumors and acute lymphoblastic leukemia (ALL) in children and adults. However, its major dose-limiting toxicity is peripheral neuropathy that can disrupt curative therapy. Peripheral neuropathy can also persist into adulthood, compromising quality of life of childhood cancer survivors. Reducing VCR-induced neurotoxicity without compromising its anticancer effects would be ideal. Here, we show that low expression of NHP2L1 is associated with increased sensitivity of primary leukemia cells to VCR, and that concomitant administration of VCR with inhibitors of NHP2L1 increases VCR cytotoxicity in leukemia cells, prolongs survival of ALL xenograft mice, but decreases VCR effects on human-induced pluripotent stem cell-derived neurons and mitigates neurotoxicity in mice. These findings offer a strategy for increasing VCR's antileukemic effects while reducing peripheral neuropathy in patients treated with this widely prescribed medication.
Identifiants
pubmed: 33742760
doi: 10.1111/cts.13012
pmc: PMC8301581
doi:
Substances chimiques
Ribonucleoproteins, Small Nuclear
0
Snu13 protein, human
0
Vincristine
5J49Q6B70F
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
1490-1504Subventions
Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States
Organisme : NIH HHS
ID : R01 MH097742
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA036401
Pays : United States
Organisme : ALSAC
Organisme : NIH HHS
ID : U01 GM92666
Pays : United States
Organisme : NIH HHS
ID : R21 CA222764
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097742
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM092666
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC012833
Pays : United States
Informations de copyright
© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
Références
Neuromuscul Disord. 2017 May;27(5):439-446
pubmed: 28284873
Cancer Res. 1988 Oct 1;48(19):5585-90
pubmed: 3416311
Br J Clin Pharmacol. 2011 Oct;72(4):634-46
pubmed: 21649691
Cell Death Differ. 2015 Dec;22(12):1946-56
pubmed: 26024389
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9552-6
pubmed: 8105478
Curr Mol Pharmacol. 2020 Apr 27;:
pubmed: 32342825
EMBO Rep. 2014 Sep;15(9):948-55
pubmed: 25092791
Cancer Chemother Pharmacol. 1999;44(3):203-9
pubmed: 10453721
Blood. 1997 Oct 1;90(7):2723-9
pubmed: 9326239
Pharmacol Rev. 1995 Jun;47(2):331-85
pubmed: 7568331
JAMA. 2015 Feb 24;313(8):815-23
pubmed: 25710658
EMBO J. 2014 Nov 18;33(22):2623-42
pubmed: 25257310
Front Pharmacol. 2020 May 01;11:567
pubmed: 32425794
J Biol Chem. 1986 May 15;261(14):6137-40
pubmed: 3700389
J Child Adolesc Psychopharmacol. 2018 Jul/Aug;28(6):379-386
pubmed: 29847157
Nucleic Acids Res. 2010 Oct;38(18):6274-85
pubmed: 20466811
Stem Cell Res. 2017 Jul;22:79-88
pubmed: 28645005
EMBO Rep. 2014 Sep;15(9):956-64
pubmed: 25092792
Proc Natl Acad Sci U S A. 1986 Jun;83(11):3847-50
pubmed: 3459160
Curr Top Med Chem. 2015;15(9):822-9
pubmed: 25697566
Science. 2007 Apr 6;316(5821):115-20
pubmed: 17412961
Biostatistics. 2003 Apr;4(2):249-64
pubmed: 12925520
Lancet Child Adolesc Health. 2018 Oct;2(10):744-754
pubmed: 30236383
Leuk Lymphoma. 1998 Sep;31(1-2):195-208
pubmed: 9720729
Nature. 2010 Apr 1;464(7289):721-7
pubmed: 20360735
Mol Cell. 2000 Dec;6(6):1331-42
pubmed: 11163207
Leukemia. 2009 Sep;23(9):1564-76
pubmed: 19421227
J Neurosci Methods. 1994 Jul;53(1):55-63
pubmed: 7990513
Blood. 1997 Apr 15;89(8):2959-65
pubmed: 9108416
J Natl Cancer Inst. 2013 Sep 4;105(17):1322-31
pubmed: 23940287
PLoS One. 2015 Feb 17;10(2):e0118020
pubmed: 25689802
N Engl J Med. 2004 Aug 5;351(6):533-42
pubmed: 15295046
SLAS Discov. 2018 Feb;23(2):164-173
pubmed: 28985478
J Clin Invest. 2002 Jul;110(1):91-9
pubmed: 12093892
Nat Commun. 2018 Oct 31;9(1):4541
pubmed: 30382096
Biochem Pharmacol. 1973 Sep 1;22(17):2113-9
pubmed: 4126253
Br J Cancer. 1991 Oct;64(4):705-9
pubmed: 1680368
Clin Pharmacol Ther. 2003 Jan;73(1):51-60
pubmed: 12545143
Clin Pharmacokinet. 1999 Oct;37(4):273-87
pubmed: 10554045
Pharmacol Ther. 2005 Apr;106(1):1-18
pubmed: 15781119
J Neurol Sci. 1970 Feb;10(2):107-31
pubmed: 4314181
Br J Cancer. 1987 Oct;56(4):413-7
pubmed: 3479994
J Hematol Oncol. 2019 Nov 26;12(1):123
pubmed: 31771633
J Paediatr Child Health. 2011 Dec;47(12):875-82
pubmed: 21658147
Nat Rev Cancer. 2004 Apr;4(4):253-65
pubmed: 15057285
Pharmacol Res. 2014 Sep;87:144-50
pubmed: 24861566
Science. 2020 Aug 14;369(6505):858-862
pubmed: 32792401
Anesthesiology. 2000 Jun;92(6):1603-16
pubmed: 10839909
Stem Cell Res. 2016 Jan;16(1):140-8
pubmed: 26774046
EMBO J. 2014 Nov 18;33(22):2601-3
pubmed: 25266476