In vitro Cytocidal Effect of L-Glutaminase on Leukaemic Lymphocytes

Abstract

MOUSE lymphomas, such as 6C3HED, undergo complete regression after one or more injections of L-asparaginase¹, and remissions have been reported in some patients with acute leukaemia after treatment with L-asparaginase^2–4. Roberts et al.⁵ found that purified bacterial L-glutaminase inhibited the growth of Ehrlich mouse carcinoma. Before considering this enzyme for therapeutic studies in man, it is necessary to study in vitro effects of the enzyme on human blood cells. Previous work⁶ demonstrated that the cells of 6C3HED lymphoma do not survive incubation with very low concentrations of L-asparaginase (1.7 mIU/ml.), while the cells of the in vivo resistant variant of 6C3HED were not killed by 170 mIU of enzyme/ml. The blood lymphocytes from patients with chronic lymphocytic leukaemia were found to be more sensitive than normal lymphocytes to incubation with 170 mIU of L-asparaginase/ml. but not as sensitive as 6C3HED mouse lymphoma which responds in vivo to the enzyme. In this study, the slide chamber method⁷ was used to compare the sensitivity of normal and leukaemic lymphocytes to glutaminase.