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Resistance to apoptosis in Fanconi's anaemia
Author(s) -
Monti Daniela,
Macchioni Sabrina,
Guido Marcello,
Pagano Giovanni,
Zatterale Adriana,
Calzone Rita,
Cossarizza Andrea,
Straface Elisabetta,
Malorni Walter,
Franceschi Claudio
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00550-4
Subject(s) - apoptosis , peripheral blood mononuclear cell , reactive oxygen species , genetic predisposition , pathogenesis , immunology , biology , cancer research , programmed cell death , cycloheximide , microbiology and biotechnology , cell culture , genetics , gene , in vitro
Fanconi's anaemia (FA) is a rare autosomal recessive disease characterised 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 study, we assessed the propensity to undergo apoptosis of peripheral blood mononuclear cells (PBMC) from Italian FA patients. Cells were challenged by 2‐deoxy‐ d ‐ribose (dRib) or TNF‐α plus cycloheximide as agents that induce apoptosis by interfering with cell redox status and mitochondrial membrane potential (MMP), and PBMC from FA patients resulted to be less prone to die than those from healthy subjects. The decreased susceptibility of FA cells to undergo apoptosis was also evident 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 alteration of unknown nature of the mechanisms favouring apoptosis is present in freshly collected cells from FA patients, and that such alteration could contribute to the pathogenesis of the disease, and particularly to the increased susceptibility to cancer.