Mechanisms of Resistance of Human Acute Leukaemia Cells to Cytosine Arabinoside

Abstract

S ummary . Biochemical differences between human acute myeloblastic leukaemia cells sensitive and resistant to cytosine arabinoside have been studied. Bone marrow cells from seven patients with leukaemia resistant to cytosine arabinoside showed deoxycytidine kinase activity either below normal or in the low normal range and the mean level of this enzyme was significantly lower in cells from resistant than sensitive cases. On the other hand, deoxycytidine deaminase activity tended to be high in resistant cells but the difference from sensitive cells was not statistically significant. Deoxycytidylate deaminase activity also did not vary significantly with degree of sensitivity to cytosine arabinoside. The free concentrations of the four deoxyribonucleoside triphosphates were, in general, lower in resistant than sensitive marrow cells. The deoxycytidine triphosphate level, however, was relatively increased in the resistant cells. We conclude that a number of biochemical changes may be present in cytosine arabinoside resistant leukaemia cells. It is likely that kinetic differences are the basis for some of these changes, and that low proliferative rate may be the major cause of cytosine arabinoside resistance. Selection of cells with raised deoxycytidine deaminase levels and relatively increased deoxycytidine triphosphte concentrations may also contribute to resistance.