title: Molecular and Cellular Mechanism of Leukemogenesis of ATL: Emergent Evidence of a Significant Role for HBZ in HTLV-1-Induced Pathogenesis.
abstract: Adult T-cell leukemia (ATL) is a leukemia derived from mature CD4(+) T cells and induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Previous studies have revealed many possible molecular and cellular mechanisms of HTLV-1-induced leukemogenesis, but it still remains unknown how HTLV-1 transforms peripheral CD4 T cells in infected individuals. Given the fact that only 2-5% of infected individuals develop ATL, HTLV-1 infection alone is not sufficient for the transformation of infected cells. Host genetic and epigenetic abnormalities and host immunological status should be considered in attempting to understand the mechanism of the oncogenesis of ATL. Nonetheless, it is obvious that HTLV-1 infection dramatically increases the risk of leukemia generation from peripheral CD4 T-cells, in which the incidence of leukemia is quite low. Furthermore, the evidence that all ATL cases retain the HTLV-1 provirus, especially the 3' region, indicates that HTLV-1-encoded genes play a critical role in leukemogenesis. Since increasing evidence indicates that the HTLV-1 bZIP factor (HBZ) gene plays a significant role in the pathogenesis of HTLV-1, we will discuss the cellular and molecular mechanism of ATL generation from the virological point of view, particularly focusing on HBZ.
authors.affiliation: Immunology Section, Division of Infectious Diseases, Imperial College, Wright-Fleming Institute, Norfolk Place, London W2 1PG, UK.
authors.forename: Yorifumi
authors.initials: Y
authors.lastname: Satou
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka