MOLECULAR-DETECTION OF PRE-ATL STATE AMONG HEALTHY HTLV-1 CARRIERS INAN ENDEMIC AREA OF JAPAN

Adult T-cell leukemia/lymphoma (ATL) usually develops after age 40 in Japan, suggesting a long latency since HTLV-I is considered to be tran smitted mainly from mothers to babies via breast milk. Our previous st udies had suggested that HTLV-I carriers who have a monoclonal integra tion of HTLV-I proviral DNA in the peripheral blood cells, designated pre-ATL, account for about 2% of healthy carriers and are at high risk of developing ATL. Their ages ranged from 32 to 80 (median 57). Never theless, many cases of pre-ATL showed a long-lasting carrier state (IO -year probability around 90%). In the present investigation we conduct ed a large-scale molecular detection of monoclonal integration in a po pulation (481 cases) of healthy carriers with ages ranging from 16 to 82 (median 49) for the purpose of clarifying the earliest onset of thi s pre-ATL state. Southern-blot analysis of DNA extracted from peripher al blood mononuclear cells revealed 6 cases (1.2%) with a monoclonal b and. All of these 6 were older than 40; no single positive case was fo und in 220 carriers under age 40. These results indicate that the mole cularly detectable pre-ATL state also develops after a long latency. T hus the pre-ATL state seems to be a subtype of ATL showing an extremel y indolent course of disease development, but not merely an early phas e of all subtypes of ATL. We propose that, in order to reveal a promot er(s) responsible for the development of ATL from the pre-ATL state, i ntensive epidemiological investigation of life style, eating habits, o ccupation and exposure to carcinogens must be conducted on this unique group prone to ATL. It is also important to perform such an epidemiol ogical study on the general population of carriers by paying special a ttention to the first 3-4 decades of each carrier's life in Japan and by comparing the data with those from carriers in different geographic al areas of the world. (C) 1995 Wiley-Liss, Inc.