Clinical Indications of Multiple Integrations of Human T-cell Lymphotropic Virus Type I Proviral DNA in Adult T-cell Leukemia/Lymphoma

In this review, we discuss the possible relationship between the clinical characteristics and the multiple integration of human T-cell lymphotropic virus type I (HTLV-I) proviral DNA in patients with adult T-cell leukemia/lymphoma (ATL). Some patients with ATL show multiple HTLV-I integrations and exhibit clinical characteristics unlike those of ATL patients who show the typical integration of a single provirus. Multiple HTLV-I integrations can be detected by Southern blotting as multiple bands having varied intensities. These multiple integration conditions can arise from one tumor cell clone carrying multiple copies of the provirus, or from multiple cell clones, each carrying one copy of the provirus. The former patients manifest an extremely aggressive clinical course with the infiltration of unusual organs such as the retina and uvea. The latter patients show an indolent clinical course with skin lesions. These findings suggest that the clinical implications for multiple HTLV-I integrations exist in ATL. This may be one of the explanations for the heterogeneous findings in the disease. Such observations may provide information linking viral integration with clinical manifestations, and improve our understanding of the pathogenesis of ATL.