Leukaemogenic mechanism of human T‐cell leukaemia virus type I

Adult T-cell leukaemia (ATL) is a neoplastic disease derived from CD4(+) T-lymphocytes and etiologically associated with human T-cell leukaemia virus type I (HTLV-I). In addition to structural genes, HTLV-I encodes regulatory and accessory genes in the pX region. Among them, Tax is thought to play a central role in leukaemogenesis through its potent transforming activity. However, since Tax is a major target of the host immune system, its expression is often lost in ATL cells, indicating Tax is dispensable in the last phase of leukaemogenesis. The HTLV-I bZIP factor (HBZ), encoded on the HTLV-I minus strand, was recently shown to be expressed in all ATL cells, and to support growth of human T-cell lines. These findings suggest that HBZ is critical to ATL onset. In addition to viral factors and genetic and epigenetic changes in cellular genes, the host immune status and genetic background also function in leukaemogenesis.