THE CHROMOSOMAL TRANSLOCATION T(X14)(Q28Q11) IN T-CELL PRO-LYMPHOCYTIC LEUKEMIA BREAKS WITHIN ONE GENE AND ACTIVATES ANOTHER

Chromosomal translocation t(X;14)(q28;q11) has been observed in patien ts with pro-lymphocytic T-cell leukaemia (T-PLL). In two cases of T-PL L, one of which was associated with Ataxia telangiectasia (AT), the ch romosomal break occurred in two different introns of a gene c6.1A, loc ated at the Xq28 locus. Fusion transcripts, consisting of 5' sequences of c6.1A and the TCR alpha constant (C) region, were expressed at hig h levels in the leukaemic cells from both patients, but in only one ca se did this fusion generate an in-frame c6.1A-C alpha mRNA. However, t he breaks within c6.1A seem to affect another gene, cd.1B, which is tr anscribed from the same CpG rich island as c6.1A but in the opposite t ranscriptional orientiation. The c6.1B gene is not damaged by the tran slocation but is transcribed in both T-PLL cases. Furthermore, c6.1B m ay lack protein coding capacity and thus this translocation might resu lt in a novel mechanism in tumorigenesis. In any event, this is the fi rst cloned gene which is implicated in pathogenesis of chronic/pro-lym phocytic leukaemia of the T-cell lineage.