Deoxycoformycin‐induced response in chronic lymphocytic leukaemia

deoxyadenosine toxicity in non‐replicating lymphocytes

R. F. Kefford*, R. M. Fox

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The occurrence of severe immunodeficiency disease in children with inherited adenosine deaminase deficiency, and reports of remission induction in T‐cell acute lymphoblastic leukaemia with the adenosine deaminase inhibitor deoxy‐coformycin, prompted a study of the effects of deoxyadenosine on resting peripheral blood lymphocytes (PBL) and chronic lymphocytic leukaemic (CLL) lymphocytes in short‐term culture. In the presence of an inhibitor of adenosine deaminase, micromolar concentrations of dAdo caused elevation of deoxyadenosine‐5′‐triphosphate (dATP) pools and in vitro lysis of non‐dividing PBL and CLL lymphocytes. This death of non‐replicating cells indicates a mechanism of deoxyadenosine toxicity independent of DNA replication and ribonucleotide reductase inhibition. Similar changes occurred in vivo in a patient with advanced CLL who responded to treatment with deoxycoformycin, 0.1 mg/kg, days 1‐5, with a fall in the WCC from 102.0 × 109/l to 6.8 × 109/l over 21 d. Therapeutic blockade of deoxyadenosine catabolism deserves further investigation both in the treatment of lymphoproliferative disease and as a method of lympholytic immunosuppression.

Original languageEnglish
Pages (from-to)627-636
Number of pages10
JournalBritish Journal of Haematology
Volume50
Issue number4
DOIs
Publication statusPublished - 1982
Externally publishedYes

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