p53 allele deletion and protein accumulation occurs in the absence of p53 gene mutation in T-prolymphocytic leukaemia and Sezary syndrome

In a series of 24 patients with chronic T-lymphoid disorders [13 T-prolymph ocytic leukaemia (T-PLL) and 11 Sezary syndrome] we have studied (i) chromo some 17p abnormalities and p53 allele deletion by fluorescence in situ hybr idization; (ii) mutation in the exons of the p53 gene by direct DNA sequenc ing: and (iii) p53 protein expression by immunocytochemistry and, in some c ases, also by now cytometry with DO-1, a monoclonal antibody to the p53 pro tein. The study revealed p53 deletion and accumulation of p53 protein in th e absence of mutation in the exons that included the hot-spots and differs from that described in B-prolymphocytic leukaemia. Seven T-PLL and five Sez ary syndrome patients had p53 overexpression, and five T-PLL and nine Sezar y syndrome patients showed p53 deletion. Although the majority of cases wit h p53 accumulation had p53 deletion, the proportion of cells with the delet ion did not correlate with the proportion of cells positive for p53 express ion. Two cases of T-PLL shelved strong p53 expression in the absence of p53 deletion, and one case of Sezary syndrome with p53 deletion in 97% of cell s did not express p53. These findings suggest that a non-mutational mechani sm exists for the accumulation of p53 protein in these T-cell disorders. Th e oncogenic effect of the accumulating wild-type protein has been reported in other malignancies. Whether haploidy resulting from p53 deletion contrib utes to this mechanism has yet to be determined. Alternatively, the frequen t loss of the p53 gene could be associated with the deletion of an adjacent gene, which could be involved in the pathogenesis of these diseases.