Defective human T-cell leukemia virus in adult T-cell leukemia patients

Human T-cell leukemia virus (HTLV) is associated with adult T-cell leukemia (ATL). We have examined the state of the HTLV provirus in the leukemic cells of ATL patients, and found that all the circulating leukemic cells of ATL proliferated monoclonally with one or more proviral integrations. Unexpectedly, we observed a high incidence of multiple integration of the provirus that also revealed a clonality and therefore occurred prior to the clonal origin of the ATL cells. Several ATL patients contained defective proviruses in fresh leukemic cells. These defective proviruses varied with respect to the deleted portions of the HTLV genome when a full genome of the HTLV provirus was present in the ATL tumor cells. In contrast, ATL cells harboring only a defective provirus invariably retained a common sequence of env-pX-LTR. This is consistent with a model that implies that the preserved env-pX-LTR region of HTLV must have played an important role(s) at a certain stage in ATL leukemogenesis after proviral integration. This is the first indication that the whole HTLV genome is not necessarily required to initiate or maintain the monoclonal proliferation of ATL leukemic cells in patients.