RESISTANCE TO APOPTOSIS IN FANCONI ANEMIA - AN EX-VIVO STUDY IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Fanconi's anaemia (FA) is a rare autosomal recessive disease character ised by progressive pancytopoenia, a diverse assortment of congenital malformations, an increased sensitivity to reactive oxygen species and a predisposition to the development of malignancies. In the present s tudy, me assessed the propensity to undergo apoptosis of peripheral bl ood mononuclear cells (PBMC) from Italian FA patients, Cells were chal lenged by 2-deoxy-D-ribose (dRib) or TNF-alpha plus cycloheximide as a gents that induce apoptosis by interfering with cell redox status and mitochondrial membrane potential (MMP), and PBMC from FA patients resu lted to be less prone to die than those from healthy subjects. The dec reased susceptibility of FA cells to undergo apoptosis was also eviden t when another parameter highly correlated with the apoptotic process, i.e. MMP, was measured. Moreover, when N-acetylcysteine was added to dRib-treated PBMC, a strong protection was evident either in PBMC from control subjects or from FA patients, These data indicate that an alt eration of unknown nature of the mechanisms favouring apoptosis is pre sent in freshly collected cells from FA patients, and that such altera tion could contribute to the pathogenesis of the disease, and particul arly to the increased susceptibility to cancer. (C) 1997 Federation of European Biochemical Societies.