Clinical implication of the integration patterns 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 integration patterns of human T-cell lymphotropic virus type I (HTLV-I) proviral DNA in patients with adult T-cell leukemia/lymphoma (ATL). Some ATL patients show unusual integration patterns such as multiple or defective HTLV-I and have clinical characteristics unlike those of most ATL patients who have the characteristic integration pattern of one complete provirus. Multiple HTLV-I integrations can be detected as two or more bands using the standard Southern blotting method when the tumor cellular DNA is digested with an endonuclease that does not cleave within the provirus. This includes cases of one tumor cell clone carrying two or more copies of the provirus, or alternatively two or more cell clones, each carrying one copy of the provirus. The former group of patients always manifest severe dyspnea and hypoxemia with unusual organ infiltrations including the retina and muscle and an extremely aggressive clinical course. On the other hand, the latter group of patients have an indolent course with skin lesions or small T lymphocytes with cleaved or lobulated nuclei. A solitary defective HTLV-I in some ATL patients can be detected as one smaller band after digestion of cellular DNA with an endonuclease that does not cleave within the provirus. These patients generally have a favourable clinical course with small cleaved or bilobulated T lymphocytes without lymphadenopathy or skin lesions. These findings suggest that there are clinical implications for the integration patterns of HTLV-I and this may be one of the explanations for the heterogeneous behaviour of the disease. Such studies may provide information on the relationship between virus integration and the clinical manifestations and also improve our understanding of the pathogenesis of ATL.