Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of 6-mercaptopurine (6-MP) in L-1210 mouse leukemia cells and human chronic myelocytic leukemia cells (CML cells) was examined. The acid-soluble fractions obtained from cells incubated with [8-14C]6-MP were chromatographed on a Dowex-1 formate resin column using a formic acid linear gradient elution system. Chromatography of the extract of L-1210 cells revealed four principal radioactive peaks. The fraction containing the third peak was hydrolyzed by snake venom 5'-nucleotidase (Crotalus adamanteus). Cellulose thin layer chromatography revealed that the radioactive peak of the hydrolysate corresponded to 6-thioguanosine. The results showed that 6-MP was converted to 6-thioinosinic acid (6-TIMP) and 6-thioguanylic acid (6-TGMP) in L-1210 cells. In order to elucidate the pathway of 6-MP conversion to 6-TGMP, we examined the interaction of [8-14C]6-TIMP and purified IMP dehydrogenase. It was found by DEAE-cellulose thin layer chromatography that the IMP dehydrogenase converted 6-TIMP to 6-thioxanthylic acid (6-TXMP). Dowex-1 chromatography of the acid-soluble extract of human CML cells incubated with [8-14C]-6-MP also revealed a radioactive peak corresponding to 6-TGMP. These results suggest that 6-MP is metabolized to 6-TGMP by serial conversion to 6-TIMP and 6-TXMP through the de novo GMP synthetic pathway in L-1210 cells and human CML cells.
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PMID:Conversion of 6-mercaptopurine to 6-thioguanylic acid in L-1210 cells and human leukemia cells. 285 24

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.
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PMID:Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients. 316 89

High levels of the ectozyme 5'-nucleotidase (5'-N) and the common ALL-antigen (cALLA) are coexpressed on leukemic blast cells in common ALL, in the lymphoid blast crisis of CML and also on the lymphoblastoid cell-line Nalm-1. Clinically this coexpression can help to subclassify leukemias and may be of diagnostic and prognostic significance. In an attempt to study the mechanism underlying this simultaneous expression plasmamembrane subfractionation was undertaken on Nalm-1. When membrane-shedding from intact cells is induced by sublytic concentrations of the lysophosphatidyl-choline analogue ET-12-H, membrane subfractions are obtained which contain 30-40% of total cellular 5'-N, which is most of the enzyme carried on the cell surface, in a highly enriched form. Under these conditions only a very low release of intracellular enzymes is observed. On the other hand cALLA is not accumulated in these membrane fractions to any appreciable extent. The predominant part of this antigen is still on the intact cells remaining after the shedding procedure. It is concluded that the simultaneous expression of 5'-N and cALLA on Nalm-1 and leukemic blasts is not regulated by a physical association or a close neighborhood of these antigens on the membrane level.
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PMID:Independent expression of the surface markers 5'-nucleotidase and cALLA on leukemic cells. 629 37

The enzyme 5'-nucleotidase (5'-N) was demonstrated cytochemically in blood cells using a modification of the Wachstein and Meisel technique [30]. In peripheral blood the activity was found to be localised mainly in the cell membrane of lymphocytes. A semiquantitative score of 5'-N positivity, was assessed in lymphocytes from eight normal donors and 60 patients with various types of leukaemia and lymphoma. The lymphocyte score of 5'-N was slightly reduced in CML and AML but markedly reduced in most lymphoproliferative states tested. The only supranormal activity was found in two of 18 cases of CLL.
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PMID:5'-Nucleotidase in lymphocytes from various clinical disorders. 630 May 63