Roles of AML 1/ RUNX 1 in T‐cell malignancy induced by loss of p53

AML1 / RUNX1 is a frequent target of chromosome translocations and mutations in myeloid and B‐cell leukemias, and upregulation of AML 1 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. AML 1 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 AML 1 stimulates T‐lymphocyte proliferation. These results suggest that upregulation of AML 1 induced by loss of p53 promotes lymphoid‐cell proliferation, thereby inducing lymphoma development.