title: Roles of AML1/RUNX1 in T-cell malignancy induced by loss of p53.
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.
authors.affiliation: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Kazutsune
authors.initials: K
authors.lastname: Yamagata
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Issay
authors.initials: I
authors.lastname: Kitabayashi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D013953:Thymus Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D016159:Tumor Suppressor Protein p53