Clonal evolution of malignant and non-malignant T cells carrying t(14;14) and t(X;14) in patients with ataxia telangiectasia.

People with ataxia telangiectasia (AT) are at a higher than normal risk of T cell leukaemia and often have either non-malignant or malignant T cells with chromosomal abnormalities, typically t(14;14), inversion 14 or more rarely t(X;14). This provides a chance to study the pre-leukaemic phase of the disease. T cells have been studied with either t(14;14)(q11;q32.1) or t(X;14)(q28;q11) from two AT sisters of which the latter developed T cell leukaemia. The telomeric breakpoint of the t(14;14) was cloned and found to occur at 14q32.1 where known tumour-associated breakpoints are located, but the patient remains asymptomatic for leukaemia. Analysis of T cell populations in both patients showed that the cells containing the translocation became oligoclonal with respect to T cell receptor beta rearrangement and complete T cell receptor beta clonality was only established in the patient with t(X;14) by onset of overt disease. Therefore in these chronic diseases, chromosomal translocations can precede T cell receptor rearrangement suggesting a role for these abnormalities as early events of malignant outgrowth.