Human Fanconi A cells are susceptible to TRAIL-induced apoptosis


Carlo Dufour, M.D, Haematology Unit, Department of Paediatric Haemato-Oncology, G. Gaslini Institute, Largo G. Gaslini 5, 16148 Genova, Italy.


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.