Increase in 2’,5’-Oligoadenylate Synthetase Caused by Deoxycoformycin in Hairy Cell Leukaemia

Abstract

Introduction: Deoxycoformycin (dCF) is a potent inhibitor of the enzyme adenosine deaminase (ADA). Although used initially to treat T-cell leukaemias, dCF has also been found to be effective in the treatment of hairy cell leukaemia (HCL) (Spiers et al, 1984). Inhibition of ribonucleotide reductase by accumulation of dATP is thought to be the dominant mechanism of toxicity of dCF in rapidly proliferating cells as in T-acute lymphoblastic leukaemia (T-ALL)(Mitchell et al, 1983) but how dCF kills slowly proliferating cells such as in HCL and other chronic B or T-cell tumours is unclear. In these diseases no definite correlation has been found between clinical response and the results of in vivo or in vitro studies of some postulated mechanisms of cytotoxicity including depletion of nicotinamide adenine dinucleotide (NAD) or ATP, accumulation of DNA strand breaks or of dATP. However, a correlation of clinical response with decreased S-adenosyl-homocysteine hydrolase (SAHH) levels has been shown (Ganeshaguru et al, 1987, Ho et al, 1988).KeywordsAdenosine DeaminaseNicotinamide Adenine DinucleotideHairy Cell LeukaemiaHairy CellOLIGOADENYLATE SynthetaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.