Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A multienzyme complex containing at least DNA polymerase (EC 2.7.7.7), thymidine kinase (EC 2.7.1.21), dTMP kinase (EC 2.7.4.9) nucleoside diphosphokinase (EC 2.7.4.6) and thymidylate synthetase was separated from the corresponding free enzymes of DNA precursor synthesis by gel filtration of a gently lysed preparation of HPB-ALL cells (a human lymphoblastoid cell line). The isolated incorporated the distal DNA precursors [3H]thymidine or [3H]dTMP into an added DNA template at rates comparable to those observed using the immediate precursor [3H]dTTP. Measurement of the apparent overall concentrations of [3H]dTTP produced during incorporation of [3H]thymidine and of [3H]dTMP were so low as to suggest that these precursors were channelled into DNA by the operation of a kinetically linked complex of precursor-synthesizing enzymes and of DNA polymerase. The DNA polymerase inhibitor 1-beta-D-arabinofuranosylcytosine triphosphate reduced incorporation of distal precursors into DNA. However [3H]dTTP did not accumulate in the reaction mixture. This suggested that the DNA polymerase regulated the flow of substrates through the complex. The results in this paper constitute direct evidence for the existence of multienzyme complexes of DNA synthesis in mammalian cells.
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PMID:Gel filtration of a complex of DNA polymerase and DNA precursor-synthesizing enzymes from a human lymphoblastoid cell line. 630 81

The cellular levels of the purine catabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and those for the pyrimidine activities thymidine phosphorylase and thymidine kinase isozymes have been measured concurrently in peripheral blood nucleated cells of patients with acute lymphoblastic leukaemia, chronic lymphocytic or prolymphocytic leukaemia and correlated with the spontaneous tritiated thymidine uptake of the isolated cells. Highest ADA levels occurred in T-ALL cells but considerable overlap of individual activities occurred for non-T, non-BALL, B-CLL and T-CLL cells. The levels of PNP showed no distinct discriminatory trend in cells of the lymphoid proliferative disorders examined. Thymidine phosphorylase activity was markedly reduced in T-ALL and T-CLL cells with a stepwise increase in the level of mean activities for non-T, non-B ALL, B-CLL and B-PLL cells to that of isolated normal peripheral blood lymphocytes. Spontaneous tritiated thymidine uptake of the abnormal lymphoid cells exhibited a correlation between cellular thymidine kinase isozyme 1 and elevated ADA levels. The use of ADA inhibitors together with thymidine infusion for the treatment of lymphoproliferative disorders is discussed.
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PMID:Purine and pyrimidine activities in acute and chronic lymphocytic leukaemia: relation to cellular proliferative status. 681 8

To control severe GvHD while maintaining strong GvL effects in the context of allo-stem cell transplantation (allo-SCT), a phase I/II clinical trial of infusions of donor lymphocytes transduced with the herpes simplex virus thymidine kinase (TK-DLI) started at the Tsukuba University Hospital. To date, five (2 AML, 2 ALL, and 1 MDS) out of eight patients enrolled in the trial received approximately 7x10(7) transduced cells per kilogram of body weight and four patients showed some clinical responses such inhibition of the leukemic cell proliferation or mitigation of lymph node swelling. Especially, one MDS patient achieved complete remission and has remained in CR for 2 years after the treatment. GvHD developed in two patients (1 acute and 1 chronic) and the acute (grade III) was successfully controlled by administration of ganciclovir without any immunosuppressive drugs. Since HSV-TK as a strong antigen induced CTLs against transduced cells in patients, however, TK-DLI is expected to provide a more effective adoptive immune cell therapy by performance just after allo-SCT where the patient's immune function is severely damaged.
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PMID:Gene and cell therapy for relapsed leukemia after allo-stem cell transplantation. 1850 42