Distinct oncogenic phenotypes in hematopoietic specific deletions of Trp53.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 05 2023
09 05 2023
Historique:
received:
27
08
2022
accepted:
21
04
2023
medline:
11
5
2023
pubmed:
10
5
2023
entrez:
10
5
2023
Statut:
epublish
Résumé
Loss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. In order to dissect the role of P53 in the hematopoietic system, we generated and analyzed two different mouse models deficient for P53. A pan-hematopoietic P53 deletion mouse was created using Vav1-Cre based deletion; and a B-cell-specific deletion mouse was created using a CD19-Cre based deletion. The Vav1-P53CKO mice predominantly developed T-cell malignancies in younger mice, and myeloid malignancies in older mice. In T-cell malignancies, there was accelerated thymic cell maturation with overexpression of Notch1 and its downstream effectors. CD19-P53CKO mice developed marginal zone expansion in the spleen, followed by marginal zone lymphoma, some of which progressed to diffuse large B-cell lymphomas. Interestingly, marginal zone and diffuse large B-cell lymphomas had a unique gene expression signature characterized by activation of the PI3K pathway, compared with wild type marginal zone or follicular cells of the spleen. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.
Identifiants
pubmed: 37160922
doi: 10.1038/s41598-023-33949-8
pii: 10.1038/s41598-023-33949-8
pmc: PMC10169790
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Tumor Suppressor Protein p53
0
Adaptor Proteins, Signal Transducing
0
Antigens, CD19
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7490Subventions
Organisme : NIH HHS
ID : T32CA009120
Pays : United States
Organisme : NIH HHS
ID : T32 CA009056
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA166450
Pays : United States
Organisme : NIH HHS
ID : K08AR072787
Pays : United States
Organisme : NIH HHS
ID : R01CA264986
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM109146
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA264986
Pays : United States
Informations de copyright
© 2023. The Author(s).
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