in the absence of normal TCR/MHC signaling A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma

Abstract Stat5 proteins are critical signaling molecules activated by many cytokines. Within the immune system, Stat5 plays important roles related to the development of thymocytes and proliferation of T-cells. Stat5 has been implicated in malignant transformation, and moreover, the activated tyrosine phosphorylated form of Stat5 is frequently observed in human lymphomas. We previously demonstrated the oncogenic potential of Stat5, with thymic lymphoblastic lymphomas developing in a significant proportion of transgenic (TG) mice over-expressing Stat5a or Stat5b in lymphocytes. In addition, immunization or expression of a T-cell receptor (TCR) transgene augmented the rate of tumor formation. Here we investigate the mechanism of Stat5-mediated lymphomagenesis by exploring the contributions of MHC/TCR and pre-TCR signals. We present data demonstrating that Stat5b TG mice unexpectedly develop CD8 + lymphoma even in the absence of either pre-TCR signaling or normal thymic selection. Indeed, acceleration of Stat5b TG-mediated lymphoma occurred on TCRα