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However, the pathophysiological functions of VAV1\u2010MYO1F in lymphomagenesis are insufficiently defined. Therefore, we generated transgenic mouse models to conditionally express VAV1\u2010MYO1F in T\u2010cells in vivo. We demonstrate that VAV1\u2010MYO1F triggers cell autonomous activation of T\u2010cell signaling with an activation of the ERK, JNK, and AKT pathways. VAV1\u2010MYO1F expression induces a T\u2010cell activation phenotype with high surface expression of CD25, ICOS, CD44, PD\u20101, and decreased CD62L as well as aberrant T\u2010cell differentiation, proliferation, and neoplastic transformation. Consequently, the VAV1\u2010MYO1F expressing T\u2010cells induce a malignant T lymphoproliferative disease with 100% penetrance in vivo that mimics key aspects of human peripheral T\u2010cell lymphoma. 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