Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia

Abstract

A recently developed deoxythymidine kinase assay, utilizing iodine‐125‐iodo‐deoxyuridine as substrate and capable of detecting enzyme activity in serum from healthy humans, was used in an investigation of sera from 55 untreated patients with chronic lymphocytic leukemia (CLL). When confined to the study, the patients were classified as having progressive or indolent disease and according to Rai stage. The results showed a significant correlation between serum deoxythymidine kinase activity (S‐TK) and disease status, i.e., higher values were found in patients with progressive disease, compared to those with indolent disease. S‐TK also correlated with Rai stage. S‐TK values of more than 40 times the normal value were found in some patients. All patients with S‐TK > 8.4 units had a disease that was or became progressive during the observation period. Within the patient group with indolent disease two groups that differed with regard to prognosis could be distinguished according to their initial S‐TK values. In longitudinal studies of 18 patients with indolent disease, S‐TK was found to exceed 8.4 units only on one occasion during an observation period of up to 68 months. In patients with indolent disease, a transition to progressive disease was parallelled by an increase in S‐TK. Studies of S‐TK levels in 18 patients receiving treatment showed that S‐TK decreased during successful therapy. S‐TK was also found to increase when the disease was reactivated. From these results it is concluded that S‐TK could be used as a prognostic marker for the individual CLL patient. Furthermore, S‐TK seems to be useful for longitudinal follow‐up studies of disease status, both in indolent disease and in progressive disease during treatment.

Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL

“…The predominant form of TK is present in dividing cells and absent in nondividing cells; thus, this enzyme is a potentially useful marker of proliferative activity. Early studies reported that elevated TK levels correlated with advanced Rai stage and progressive disease, 65 and, on retrospective analysis, untreated patients with indolent disease could be separated into 2 prognostic groups on the basis of their initial serum TK. In a more recent study of 113 patients with CLL, TK was an independent prognostic variable on multivariate analysis; however, this study did not include assessment of IgV H mutation status, CD38, or chromosome analysis by FISH.…”

An optimized whole blood method for flow cytometric measurement of ZAP‐70 protein expression in chronic lymphocytic leukemia

“…, serum CD23 (3), serum CD44 (4), serum thymidine kinase (5), and a number of cytogenetic markers (6). Studies originally aimed at understanding the level of maturation of B-cell CLLs demonstrated that these leukemias variably expressed restricted sets of immunoglobulin genes, in either the germ-line (indicative of relatively immature) or mutated (more mature) configuration (7).…”

Serum thymidine kinase, a possible marker for monitoring the effect of bone marrow transplant treatment in early recovery phase

“…Clinical application of the Prolifigen TK-REA technique was previously reported by several authors in patients with malignant disorders and those with non-malignant disorders. [3][4][5][6][7][8][9][10][11][12][13][14][15] Hogberg et al 12 suggested that the bone marrow cells in patients with B 12 deficiency have a defect in DNA synthesis, resulting in the accumulation of immature proliferating bone marrow cells locked at the stage of TK production and release. In a study of patients with untreated B,2 deficiency, serum TK activity was found to be closely correlated with the extent of bone marrow insufficiency, with very high levels being observed in those with the most severe haematological disorders.…”