TCL1 ONCOGENE ACTIVATION IN PRELEUKEMIC T-CELLS FROM A CASE OF ATAXIA-TELANGIECTASIA

The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosom e translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inve rsions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias , such as T-prolymphocytic (T-PLL). It is also involved in T-acute and -chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome. Similar chromosomal rearrangements occur a lso in the clonally expanded T cells in AT patients before the appeara nce of the overt leukemia, We have analyzed the expression of TCL1 mRN A and protein in peripheral blood lymphocytes (PBLs) from four AT case s and from healthy controls, We found that the TCL1 gene was overexpre ssed in the PBLs of an AT patient with a large clonal T-cell populatio n exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases. Fluorescence in situ hybridization of the TCL1 genomi c locus to lymphocyte metaphases from the AT patient with the T-cell c lonal expansion showed that the breakpoint of the t(14;14) translocati on lies within the TCL1 locus and is accompanied by an inverted duplic ation of the distal part of chromosome 14, These data indicate that TC L1 is activated in preleukemic clonal cells as a consequence of chromo some translocation involving sequences from the TCR locus at 14q11. De regulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinic al evaluation. (C) 1995 by The American Society of Hematology.