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- Title
In vitro andin vivo effects of 2′-deoxycoformycin (Pentostatin) on tumour cells from human γδ[sup +] T-cell malignancies.
- Authors
Aldinucci, Donatella; Poletto, Dalisa; Zagonel, Vittorina; Rupolo, Maurizio; Degan, Massimo; Nanni, Paola; Gattei, Valter; Pinto, Antonio
- Abstract
Summary. Hepatosplenic gamma delta[sup +] T-cell lymphoma represents a rare neoplasm of post-thymic phenotype, characterized by an aggressive clinical course and a poor response to conventional chemotherapy. In the present study, we have examined the cytotoxic effects of the purine analogue 2'-deoxycoformycin (dCF) on cultured mononuclear cells and purified gamma delta[sup +] tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic gamma delta[sup +] T-cell lymphoma. At a concentration of 10 micro M, dCF, in the presence of 2'-deoxyadenosine (dAdo), displayed an early and selective cytotoxic effect on gamma delta[sup +] tumour T cells. After 48 h of in vitro exposure to dCF, the absolute number of viable CD3[sup +]/gamma delta[sup +] tumour T cells was reduced by more than 90% in all samples with respect to control cultures, with absolute counts of viable CD3[sup +]/alpha beta[sup +] lymphocytes being reduced only by 6-40% of the initial cell input. Analysis of cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of normal CD3[sup +]/alpha beta[sup +] T cells, which accounted, however, for only 20-25% of the initial cell input. Accordingly, the combination of dCF (10-100 micro M) plus dAdo was able to induce a dose-dependent inhibition of clonogenic growth and [[sup 3]H]-thymidine incorporation in purified CD3[sup +]/CD4[sup -]/CD8[sup -] gamma delta[sup +] tumour cells. We also report that one patient with hepatosplenic gamma delta[sup +] T-cell lymphoma in terminal leukaemic phase showed a striking haematological response to single-agent dCF given as fourth-line treatment. In particular, the selective clearance of gamma delta[sup +] tumour T cells in peripheral blood and bone marrow was observed starting after the second course of treatment. Our results suggest that dCF may represent a potentially active drug for the management of this aggressive form of T-cell lymphoma.
- Subjects
PURINES; T cells; CELL-mediated cytotoxicity; THERAPEUTICS
- Publication
British Journal of Haematology, 2000, Vol 110, Issue 1, p188
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2000.02129.x