Leukemogenesis of adult T-cell leukemia.

Adult T-cell leukemia (ATL) is one of the most aggressive hematologic malignancies and is caused by human T-cell leukemia virus type I (HTLV-I). Tax, encoded by the HTLV-I pX region, has been recognized by its pleiotropic actions as a critical accessory protein playing a central role in leukemogenesis. However, fresh ATL cells frequently lose Tax protein expression via several mechanisms, such as genetic and epigenetic changes in the provirus. Furthermore, there is a long latency period before the onset of ATL, indicating the multistep mechanisms of leukemogenesis. Therefore, additional factors, including other viral proteins, genetic and epigenetic changes of the host genome, and alterations in the gene expression and immune systems of the host cells, may be implicated in ATL leukemogenesis. This review summarizes recent advances in the understanding of ATL leukemogenesis.