title: Resistance to apoptosis in Fanconi's anaemia. An ex vivo study in peripheral blood mononuclear cells.
abstract: 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-alpha 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.
authors.affiliation: Department of Biomedical Sciences, University of Modena, Italy. montidan@unimo.it
authors.forename: D
authors.initials: D
authors.lastname: Monti
authors.forename: S
authors.initials: S
authors.lastname: Macchioni
authors.forename: M
authors.initials: M
authors.lastname: Guido
authors.forename: G
authors.initials: G
authors.lastname: Pagano
authors.forename: A
authors.initials: A
authors.lastname: Zatterale
authors.forename: R
authors.initials: R
authors.lastname: Calzone
authors.forename: A
authors.initials: A
authors.lastname: Cossarizza
authors.forename: E
authors.initials: E
authors.lastname: Straface
authors.forename: W
authors.initials: W
authors.lastname: Malorni
authors.forename: C
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003513:Cycloheximide / Q000494:pharmacology; D003855:Deoxyribose / Q000494:pharmacology; D005199:Fanconi Anemia / Q000473:pathology*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003855:Deoxyribose; D003513:Cycloheximide