COMPARATIVE-EVALUATION OF DIEPOXYBUTANE SENSITIVITY AND CELL-CYCLE BLOCKAGE IN THE DIAGNOSIS OF FANCONI-ANEMIA

Fanconi anemia (FA) is a clinically and genetically heterogenous disea se that is usually diagnosed on the basis of chromosomal instability r eflecting the hypersensitivity towards the DNA cross-linking agents di epoxybutane (DEB) and/or mitomycin C. A less well-known cellular featu re that characterizes FA patients is an intrinsic cell cycle disturban ce consisting of prolonged progression through, and arrest within, the G2 phase compartment of the cell cycle. In a collaborative blind stud y, we have evaluated 72-hour lymphocyte cultures from 66 patients with clinical suspicion of FA both for DEB sensitivity and cell cycle dist urbance, A concordant result was obtained in 63 of 66 cases. Each of t he 3 discordant, but only 1 of the concordant cases presented with ove rt leukemia, Seventeen cases were identified as classical FA because o f their increased DEB sensitivity and G2 phase blockage. Five cases sh owed a cell cycle disturbance but only borderline DEB sensitivity, The se cases might represent atypical or nonclassical forms of FA. They wo uld have been missed by cell cycle studies without concomitant DEB tes ting. Used in conjunction, cytogenetic and flow cytometric testing pro vide for the currently optimal diagnosis of FA in nonleukemic patients . (C) 1995 by The American Society of Hematology.