title: Increase in 2',5'-oligoadenylate synthetase caused by deoxycoformycin in hairy cell leukaemia.
abstract: 2',5'-oligoadenylate synthetase (2-5OAS) has been studied in peripheral blood mononuclear cells from nine patients with hairy cell leukaemia (HCL) receiving therapy with the adenosine deaminase inhibitor deoxycoformycin (dCF) or alpha interferon (alpha-IFN). 2-5OAS mRNA was assayed by dot-blot hybridization. Increase of 2-5OAS mRNA level was seen in six patients with HCL treated with dCF and in one patient treated with alpha-IFN who responded to therapy. A patient with a variant form of HCL treated with dCF and the second patient treated with alpha-IFN did not show an increase of 2-5OAS mRNA and neither responded to therapy. The 15 other patients with T or B-chronic lymphoblastic leukaemia (CLL), T-acute lymphoblastic leukaemia (ALL), adult T-cell leukaemia lymphoma (ATLL), non-Hodgkins lymphoma (NHL), Sezary and T or B-prolymphocytic leukaemia (PLL) treated with dCF did not show an increase in 2-5OAS, though four patients, all with T-cell tumours, responded clinically. 2-5OAS activity is known to be stimulated by alpha-IFN and recent work suggests that this rise in 2-5OAS may result in increased cleavage of mRNA for tumour necrosis factor (TNF) and other cytokines on which autocrine growth and proliferation of the tumour cells are dependent. By analogy, we suggest that one mechanism of action of dCF in hairy cell leukaemia may be to break down an autocrine growth loop for TNF or other cytokines. An alternative explanation for these observations is that cytokines released from hairy cells in the bone marrow killed by dCF induce a rise in 2-5OAS in circulating leucocytes.
authors.affiliation: Department of Haematology, Royal Free Hospital School of Medicine, London.
authors.forename: K
authors.initials: K
authors.lastname: Ganeshaguru
authors.forename: W C
authors.initials: WC
authors.lastname: de Mel
authors.forename: G
authors.initials: G
authors.lastname: Sissolak
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
authors.forename: C E
authors.initials: CE
authors.lastname: Dearden
authors.forename: A B
authors.initials: AB
authors.lastname: Mehta
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects*; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000188:drug therapy / Q000201:enzymology*; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects
chemical_list: D016898:Interferon-alpha; D012333:RNA, Messenger; D015649:Pentostatin; D015088:2',5'-Oligoadenylate Synthetase