Cytogenetic implication in adult T-cell leukemia. A hypothesis of leukemogenesis

The close association between adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) has been established. Nevertheless, the mechanism of progression of ATL by HTLV-I infection is still uncertain, because the virus contains no typical oncogene and no significant expression of the viral RNA has been generally found. I propose a model of leukemogenic process in ATL based on our cytogenetic data and molecular results in the literature. It seems that the rearrangement of some proto-oncogene and alpha-chain gene of the T-cell antigen receptor (TCR-alpha) is necessary for the development to overt ATL. A deficiency in the rearrangement of proto-oncogene to TCR-alpha may result in only a minor proliferation of abnormal lymphocytes and remain in the preleukemic state of ATL or in the HTLV-I carrier state.