Characterization of mutant clones lacking T-cell receptor alleles in a cell line from an adult T-cell leukaemia patient

Kusunoki Y, Kyoizumi S, Umeki S, Hirai Y, MacPhee DG
Br J Haematol 114(2):485-7, 2001

Summary

Infection with the human T-cell lymphotropic virus type 1 (HTLV-1) appears to lead to frequent insertion of viral DNA into the human genome, and as a result may be responsible for a degree of genetic instability in the cells concerned. We sought to test this hypothesis by attempting to characterize a set of 12 independent T-cell receptor (TCR) gene mutants recently isolated from SH-3, a cell line that we originally derived from an adult T-cell leukaemia patient in the mid 1980s. Nine of the 12 mutant clones isolated from SH-3 contained only TCR alpha in their cytoplasm while the remaining three appeared to express only TCR beta. All nine clones found to be deficient in cytoplasmically-located TCR beta protein also appeared to be totally devoid of both the TCR beta gene sequence and its corresponding TCR beta mRNA. Multiple copies of the HTLV-1 genome were detected in the chromosomal DNA of four of the 12 TCR mutant clones that we characterized in detail. Our results therefore support the hypothesis that infection of human T cells with HTLV-1 leads to genetic instability of a sort that causes significantly enhanced levels of deletion formation and the concomitant induced inactivation of a range of chromosomal genes.