Application of HTLV-1 tax transgenic mice for therapeutic intervention.

Adult T-cell leukemia-lymphoma (ATL) is a refractory T-cell malignancy caused by infection of human T-cell leukemia virus type I (HTLV-I). Although the pathogenesis of ATL remains unclear, HTLV-1 oncoprotein Tax plays an important role in pathogenesis (Matsuoka, 2003; Jeang et al., 2004). Chemotherapy resistance of ATL leads the poor prognosis of this disease. In order to understand the pathogenesis and establish an animal model useful for therapy attempts, we have generated HTLV-1 Tax transgenic mice using the Lck proximal promoter to restrict the Tax expression in T-cells. The HTLV-1 Tax transgenic mice developed diffuse large-cell lymphomas and leukemia with the similar features of a clinical, pathological and immunological characteristic of acute ATL. The fulminant disease also developed rapidly in SCID mice after engraftment of mouse ATL cells derived from the transgenic mice. In this review, we introduce the therapeutic attempts using this animal model and discuss the possible signaling pathway for a therapeutic target.