Roles of AML1/RUNX1 in T-cell malignancy induced by loss of p53.
Cancer Sci
; 104(8): 1033-8, 2013 Aug.
Article
in En
| MEDLINE
| ID: mdl-23679839
ABSTRACT
AML1/RUNX1 is a frequent target of chromosome translocations and mutations in myeloid and B-cell leukemias, and upregulation of AML1 is also observed in some cases of T-cell leukemias and lymphomas. This study shows that the incidence of thymic lymphoma in p53-null mice is less frequent in the Aml1(+/-) than in the Aml1(+/+) background. AML1 is upregulated in p53-null mouse bone-marrow cells and embryonic fibroblasts. In the steady state, p53 binds to and inhibits the distal AML1 promoter. When the cells are exposed to stresses, p53 is released from the distal AML1 promoter, resulting in upregulation of AML1. Overexpression of AML1 stimulates T-lymphocyte proliferation. These results suggest that upregulation of AML1 induced by loss of p53 promotes lymphoid-cell proliferation, thereby inducing lymphoma development.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymus Neoplasms
/
T-Lymphocytes
/
Tumor Suppressor Protein p53
/
Core Binding Factor Alpha 2 Subunit
Limits:
Animals
Language:
En
Journal:
Cancer Sci
Year:
2013
Document type:
Article
Affiliation country:
Japan