Aberrant expression of caspase cascade regulatory genes in adult T-cell leukaemia: survivin is an important determinant for prognosis

Derangement of either apoptosis or cell division is known to play an import ant role in tumorigenesis. Fas-mediated apoptosis on normal and leukaemic T cells is finely tuned by inhibitory proteins, such as FAP-1, FLIP and surv ivin, and defective caspase isoform which can attenuate the function of its intact caspase as a decoy molecule. However, complex involvement of such i nhibitors in tumour biology relating to apoptotic pathology remains unclear in the neoplasms. We report the aberrant expression of FAP-1, FLIP and sur vivin mRNAs on leukaemic T cells from adult T-cell leukaemia (ATL) patients . Among these inhibitors, only survivin was aberrantly expressed in all ATL cases, but not in any normal peripheral blood mononuclear cells (PBMCs). F urthermore, survivin mRNA expression level was characteristic in each subty pe of ATL and represented an important determinant for ATL prognosis. Howev er, the apoptotic effector of casp-8, which is essential in Fas-mediated si gnal transduction, was dominant in defective casp-8 rather than intact casp -8 in ATL cells, suggesting a favourable biological situation for escape fr om apoptosis. Taken together, ATL cells probably possess many different reg ulatory mechanisms in order to attenuate Fas-mediated signalling and subseq uently expand their populations under escape from apoptosis. Among these in hibitors, survivin is a useful bio-marker to assess tumour biology and may be a potential new target for apoptosis-based selective therapy in neoplasm s as the expression is a general feature of neoplasia, but not normal tissu es.