PRMT5-mediated H4R3sme2 Confers Cell Differentiation in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia.
Adolescent
Animals
Biomarkers
Cell Differentiation
/ genetics
Cell Line, Tumor
Child
Child, Preschool
Disease Models, Animal
Epigenesis, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Histones
/ metabolism
Humans
Immunophenotyping
Male
Mice
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
/ etiology
Protein-Arginine N-Methyltransferases
/ metabolism
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
22
07
2018
revised:
28
11
2018
accepted:
07
01
2019
pubmed:
13
1
2019
medline:
30
5
2020
entrez:
13
1
2019
Statut:
ppublish
Résumé
Little is known about the function of histone arginine methylation in acute lymphoblastic leukemia (ALL). The objective was to evaluate whether protein arginine methyltransferase 5 (PRMT5) plays a role in pediatric ALL and to determine the possible mechanism of epigenetic regulation. We used bone marrow samples from patients with pediatric ALL, the Nalm6 cell line, mature B-cell lines, and mouse xenograft models to evaluate the function of PRMT5 in ALL tumorigenesis. This study showed that PRMT5 and the symmetric dimethylation of H4R3 (H4R3sme2) were upregulated in most initially diagnosed ( We demonstrate that enhanced PRMT5 promotes BCP-ALL leukemogenesis partially by the dysregulation of B-cell lineage differentiation. H4R3sme2 and PRMT5 may serve as potential sensitive biomarkers of pediatric BCP-ALL. Suppression of the activation of PRMT5 may offer a promising therapeutic strategy against pediatric BCP-ALL.
Identifiants
pubmed: 30635341
pii: 1078-0432.CCR-18-2342
doi: 10.1158/1078-0432.CCR-18-2342
doi:
Substances chimiques
Biomarkers
0
Histones
0
PRMT5 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2633-2643Informations de copyright
©2019 American Association for Cancer Research.