Studies on the biochemical sequelae of therapy in Thy-acute lymphoblastic leukaemia with the adenosine deaminase inhibitor 2' deoxycoformycin

British Journal of Haematology
N RussellA V Hoffbrand

Abstract

In four patients with Thy-acute lymphoblastic leukaemia changes in blast cell deoxynucleoside triphosphate concentrations and, in three, changes in blast cell S-adenosyl homocysteine hydrolase activity were measured during treatment with 2' deoxycoformycin, a potent inhibitor of adenosine deaminase. These studies were aimed at identifying the molecular basis of cell killing by this drug. In three patients an increase in blast deoxyadenosine triphosphate (dATP) concentration occurred which was found to be temporally related to cell killing and was accompanied by decreased concentrations of the other three deoxyribonucleoside triphosphates. In the one patient with Thy-ALL who responded poorly to treatment, the increase in dATP concentration was delayed and was not accompanied by a fall in the concentrations of the other deoxyribonucleoside triphosphates. Progressive inactivation of blast cell S-adenosyl homocysteine hydrolase was found to occur in the three patients tested but was maximal only after a substantial reduction of peripheral blast cell count. These results show that 2' deoxycoformycin has a potent cytoreductive effect in Thy-ALL and suggest that the molecular basis of this toxicity is related both to the intracellular...Continue Reading

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Citations

Jan 1, 1991·Pharmacology & Therapeutics·W Plunkett, P P Saunders
Feb 1, 1985·Journal of Clinical Pathology·H G DrexlerJ Minowada
Aug 1, 1982·British Journal of Haematology·T SylwestrowiczA V Hoffbrand
Jul 1, 1986·British Journal of Haematology·J B JohnstonL G Israels
Jan 1, 1982·Leukemia Research·A LeyvaH M Pinedo
Oct 1, 1986·Archives of Sexual Behavior·A D Klassen, S C Wilsnack
Jan 1, 1985·Annals of the New York Academy of Sciences·B E ChechikE W Gelfand
Jan 1, 1984·Scandinavian Journal of Haematology·L J HallamM G Whiteside
Jan 1, 1985·Annals of the New York Academy of Sciences·J F SmythA V Hoffbrand
Jan 1, 1987·Leukemia Research·K GaneshaguruA V Hoffbrand
Jan 1, 1984·Leukemia Research·P H Ellims, G Medley
Jan 1, 1983·Leukemia Research·J P van Laarhoven, C H de Bruyn

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