The state of the art in the pathogenesis of ATL and new potential targets associated with HTLV-1 and ATL.

Almost 30 years have passed since adult T-cell leukemia (ATL) was identified as a new disease entity in Japan. During this period, its causative agent, human T-cell leukemia virus (HTLV-1), was discovered, and a crucial role of the viral product Tax in ATL leukemogenesis was demonstrated. Recently, another HTLV-1 product, HBZ, which is encoded on the negative strand, was found, and it has now become a subject of intensive research because of its possible activity in cell proliferation. It is, however, impossible to elucidate the whole process of ATL leukemogenesis by studying only HTLV-1, and aberrations of cellular genes such as tumor suppressor genes are also profoundly involved in the later stages of ATL development. In contrast with the progress in the understanding of ATL pathogenesis, more progress in developing therapy for ATL is needed, and there has been only slight improvement in the prognosis. Recently, unique therapeutic approaches targeting molecules and/or mechanisms involved in the pathogenesis have been explored, and some of them produced encouraging results that might lead to breakthrough therapies. One of these approaches, the use of monoclonal antibody against chemokine receptor CCR4, is now ongoing as a multicenter clinical trial in Japan. Here we review the state of the art regarding our understanding of ATL leukemogenesis and new potential molecular targets in ATL therapy.