Nucleoside transport in acute leukaemia and lymphoma: close relation to proliferative rate

Abstract

The proliferation of mammalian cells requires nucleosides which are provided either by de novo synthesis or by influx of nucleosides via membrane transporters with subsequent metabolic trapping. In this study the density of nucleoside transporters in freshly-isolated blast cells from patients with leukaemias and lymphomas was quantitated by equilibrium binding of 3H-nitrobenzylmercaptopurine riboside (NBMPR). In acute myeloid leukaemia (AML) the density of NBMPR binding sites on blast cells ranged from 3800 to 24,200 sites/cell and this value correlated with the 3H-thymidine labelling index (1-20%) which was used to measure proliferative rate (r = 0.80, P less than 0.001). Cells from patients with Burkitt's lymphoma, other B-cell lymphomas, T-lymphoblastic lymphoma and large cell lymphoma gave a 20-fold range of NBMPR site densities (from 3700 to 75,300 sites/cell) and site numbers correlated closely with the labelling index (r = 0.87, P less than 0.001). Non-proliferating cells from patients with chronic lymphocytic leukaemia expressed the lowest density of NBMPR binding sites (850-2900 sites/cell). Comparison of bone marrow and peripheral blood blasts confirmed the positive correlation between NBMPR binding sites and labelling index for four individual patients. In contrast, the density of NBMPR binding sites on lymphoblasts from non-T acute lymphoblastic leukaemia (ALL) was low (2300-7400 sites/cell) and showed little dependence on proliferation over a wide range of labelling indices (1-20%). No correlation was observed between NBMPR site density and cell size measured by the intracellular water space. Thus an increased proliferative rate of AML or lymphoma is associated with higher numbers of nucleoside transporters in the cell membrane.