TCL1 oncogene activation in preleukemic t cells from a case of ataxia-telangiectasia

Abstract

The TCL1 locus on chromosome 14q32.1 is frequently involved in chromosomal translocations and inversions with one of the T-cell receptor loci in human T-cell leukemias and lymphomas. Recently we have identified putative TCL1 oncogene from this region. In cases of ataxia-telangiectasia (AT), similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia. We have analyzed and the expression of TCL1 in peripheral blood lymphocytes (PBLs) from AT cases and from healthy controls. We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases carrying no t(14;14). Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphase from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14. These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11.