Cytidine Triphosphate Synthetase Activity in Lymphoproliferative Disorders1

Cytidine triphosphate synthetase (CTP synthetase) activity was measured in extracts from normal and malignant lymphoid cells. A range of enzyme activities was found in the majority of the lymphoproliferative disorders examined, with acute lymphocytic leukemia, nodular poorly differentiated lymphocytic lymphoma, and diffuse histiocytic (large cell) lymphoma (DHL) types exhibiting the widest ranges. The highest levels occurred in acute lymphocytic leukemia, nodular poorly differentiated lymphocytic lymphoma transforming to DHL, and DHL. In chronic lymphocytic leukemia and diffuse well-differentiated lymphocytic lymphoma, a narrow range was encountered, with individual values falling within that of the controls. The highest CTP synthetase levels in Hodgkin's disease were found in the clinically aggressive lymphocyte-depleted Hodgkin's disease. Statistically significant differences were found between the distributions of CTP synthetase activities in acute lymphocytic leukemia and the chronic leukemias (p < 0.01) and between favorable histological types of non-Hodgkin's lymphoma (dif fuse well-differentiated, nodular poorly differentiated, and dif fuse poorly differentiated lymphocytic lymphoma) and the un favorable DHL category (p < 0.05). It is suggested that CTP synthetase activity is a biochemical marker of the clinical aggressiveness of malignant lymphoma. There was not a close correlation (r2 = 0.52) between CTP synthetase and thymidine kinase activities, indicating that other biological factors in ad dition to cell proliferative rate influence the intracellular CTP synthetase level. Furthermore, in view of the heterogeneity of CTP synthetase activity in leukemia and lymphoma, it is likely that the preexisting enzyme level will be an important determi nant of the efficacy of the investigational antileukemic agent 3deazauridine, which is thought to act by inhibiting CTP synthe tase.