Mechanisms Underlying the Development of Murine T-Cell Lymphoblastic Lymphoma/Leukemia Induced by Total-Body Irradiation.

Simple Summary: Exposure to ionizing radiation can increase the excess risk of developing hematologic malignancies. Thymic lymphoma induced by fractionated total-body irradiation is one of the most robust models to study the biology of radiation-induced blood cancers in mice. In this review article, we will discuss results from published papers that elucidate cell-autonomous and non-cell-autonomous effects of ionizing radiation on the initiation, progression, and malignant transformation of T-lineage lymphoma/leukemia in the mouse thymus. Exposure to ionizing radiation is associated with an increased risk of hematologic malignancies in myeloid and lymphoid lineages in humans and experimental mice. Given that substantial evidence links radiation exposure with the risk of hematologic malignancies, it is imperative to deeply understand the mechanisms underlying cellular and molecular changes during the latency period between radiation exposure and the emergence of fully transformed malignant cells. One experimental model widely used in the field of radiation and cancer biology to study hematologic malignancies induced by radiation exposure is mouse models of radiation-induced thymic lymphoma. Murine radiation-induced thymic lymphoma is primarily driven by aberrant activation of Notch signaling, which occurs frequently in human precursor T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (T-ALL). Here, we summarize the literature elucidating cell-autonomous and non-cell-autonomous mechanisms underlying cancer initiation, progression, and malignant transformation in the thymus following total-body irradiation (TBI) in mice. [ABSTRACT FROM AUTHOR]