The TP53 tumor suppressor gene protects cells from malignant transformation by responding to stresses. These stresses include aneuploidy, DNA double stranded breaks (DSBs) and chromosome missegregations.
Tp53 induces apoptosis (programmed cell death) of lymphocytes with persistent DSBs at various genomic loci to prevent these DNA lesions from generating oncogenic chromosomal translocations.
While TP53 inactivation occurs less frequently in lymphoid malignancies than solid tumors, its loss is commonly associated with aggressive lymphoma subtypes characterized by increased tumor grade, treatment refractoriness and poor patient survival.
Using a transgenic mouse model, Craig H. Bassing, PhD, and researchers at the Center for Childhood Cancer Research (CCCR) demonstrated that somatic inactivation of Tp53 in hematopoietic stem cells or thymocytes predisposed mice to thymic lymphomas with translocations. These results indicated that Tp53 responses to chromosome missegregations and DSBs are critical for preventing malignant transformation of T and B lymphocytes.
Additional studies are underway to determine whether or not the transgenic mouse model developed at the CCCR may be useful as a preclinical model to evaluate new treatment approaches for B and T cell lymphomas with Tp53 inactivation.