Searching for gene responsible for adult T-cell leukemia(ATL)from human chromosome 14 at q32 region.

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Adult T cell leukemia/lymphoma(ATLL)are frequently found in southwest part of Japan, in which it has been thought to be caused by HTLV-I virus due to the close association between viral infection and ATLL.However, the fact of no gene expression on HTLV-I virus detected in leukemic cells indicates that the change of the cellular gene expression is indispensable for the genesis of ATLL.From the cytogenetic analysis, it has been reported that about 15% of ATLL cases have abnormalities of chromosome 14 at band q32 region. However, the molecular details these abnormalities were completely unknown. Thus, we have investigated 14q32 abnormalities in 50 cases of ATLL using fluorescence in situ hybridization (FISH)method to clarify the molecular details of these abnormalities and to find the region of favorite site for chromosomal aberration where genes responsible for the genesis of ATLL may be reside. As the results, we have found following points. 1)Either 2 or 3copies of amplification of 14q32 region can be found in about 60% of acute and lymphoma type of ATLL but not found in chronic type. 2)The chromosome abnormalities involved in immunogloblin heavy chain locus can be found in about 4% of ATLL cases. 3)In about 22% of ATLL cases, the chromosome rearrangement occurred in the region between TCLl and D14S16 loci. 4)There are at least three clusters of breakpoints derived from these chromosome rearrangements within this region. By conducting further investigation on one of these clusters, we have found a new gene, which we named as ATLl, is a candidate of ATLL related gene. Because the rearrangments of ATLl gene can be found in 8% of ATLL cases.