title: Human Fanconi A cells are susceptible to TRAIL-induced apoptosis.
abstract: Tumour necrosis factor (TNF) contributes to the pathogenesis of bone marrow failure in Fanconi anaemia (FA) patients. The sensitivity of haematopoietic cells from FA, complementation group A (FANCA) subjects, who represent the majority of FA patients, to TNF-related apoptosis-inducing ligand (TRAIL) is unknown. The human lymphoblastoid FANCA HSC072 cell line and the genetically corrected counterpart HSC072FANCA-neo were tested for apoptoptic response to TRAIL using flow cytometry and Western blotting. FANCA cells were more sensitive to TRAIL-induced apoptosis than their corrected counterparts, indicating that TRAIL negatively regulates haematopoietic FANCA cell lines. This effect involved poly(ADP-ribose) polymerase-1 cleavage and caspase-8 activation.
authors.affiliation: Haematology Unit, Department of Paediatric Haemato-Oncology, G. Gaslini Children's Hospital, Genoa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pigullo
authors.forename: Elisa
authors.initials: E
authors.lastname: Ferretti
authors.forename: Marina
authors.initials: M
authors.lastname: Lanciotti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Johanna
authors.initials: J
authors.lastname: Svahn
authors.forename: Laura
authors.initials: L
authors.lastname: Haneline
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.forename: Anna
authors.initials: A
authors.lastname: Corcione
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D053181:Caspase 8 / Q000378:metabolism*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005199:Fanconi Anemia / Q000473:pathology*; D052217:Fanconi Anemia Complementation Group A Protein / Q000032:analysis / Q000378:metabolism*; D052218:Fanconi Anemia Complementation Group C Protein / Q000032:analysis / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D061945:Caspase Inhibitors; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D009842:Oligopeptides; D053221:TNF-Related Apoptosis-Inducing Ligand; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053181:Caspase 8