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

5'Nucleotidase (EC 3.1.3.5), a purine pathway enzyme, occurs as a cellular ectoenzyme. Widely differing 5'N activity has been reported in different types of lymphoid cells and appears to be related to lymphocyte function, differentiation and immunological subtype. This paper reports a study on the ultrastructural distribution of 5'N in in different types of lymphoid leukemias and non-Hodgkin's lymphomas. In lymphoid leukemias, only cALL cells showed strong 5'N staining. In CLL, PLL and HCL the intensity of staining was less than in normal cells. In the NHL group, the reaction pattern was mixed. Infiltrating neoplastic cells, specially the large lymphoid cells, consistently showed very mild activity of the enzyme, whereas follicular center cells and other mature lymphocytes were characterized by moderately strong to strong 5'N activity. These results support the view that 5'N is a marker of lymphocyte cell differentiation.
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PMID:Ultrastructural localization of 5'nucleotidase in human normal and malignant lymphoid cells. 300 82

Differences in activities of the purine degradative enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'NT), have been observed among different classes of lymphoid malignancies. Recent studies have shown that hairy cell leukemia (HCL) may respond to treatment with the ADA inhibitor, 2-deoxycoformycin. This study demonstrates that the cells of HCL have significantly lower levels of ADA and 5'NT (P always less than 0.01) when compared to levels in normal B- or T-lymphocytes, but have higher levels of PNP (P less than 0.001 for both comparisons). Recent studies have shown that when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), cells of B-cell chronic lymphatic leukemia (B-CLL) acquire phenotypic characters of HCL. The authors have therefore also investigated the changes in enzyme pattern of B-CLL after incubation with TPA B-CLL cells are characterized by low levels of ADA, PNP, and 5'-NT, but TPA caused a marked increase in PNP activity (P less than 0.001, t test for paired samples), a pattern similar to HCL. The results from biochemical studies are thus in accordance with the hypothesis that HCL cells are more mature than B-CLL cells. The special enzyme profile of HCL suggests that a PNP inhibitor might also be effective in the treatment of this disease.
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PMID:Enzymes of purine metabolism in hairy cell leukemia. 301 Dec 39

More than 450 patients with hairy cell leukemia have been treated at the Scripps Clinic. Of 144 patients followed for a median of 14.2 months (range, 8.1-70 months), 123 (85%) obtained complete responses, 17 (12%) partial responses, 3 (2%) did not respond, and 1 patient was unevaluable. So far, 4 patients have relapsed at a median of 36 months (range, 12-48 months). Fever was the principal toxicity occurring in 43% of patients. Five patients resistant (3 patients) or intolerant (2 patients) to deoxycoformycin were also treated. Of these 5 patients, 4 obtained complete responses, including 2 patients resistant to deoxycoformycin, and 1 patient a partial response, suggesting a possible lack of cross-resistance between deoxycoformycin and 2-CdA in hairy cell leukemia. Other single-institution studies have documented similar response rates and toxicities. Ninety patients with advanced chronic lymphocytic leukemia were treated with 2-CdA administered either as a 0.1 mg/kg/day 7-day continuous intravenous infusion or as a 0.028-0.14 mg/kg/day 2-hour bolus for 5 consecutive days. Four patients (4%) obtained complete responses and 36 patients (40%) partial responses, using NCI-sponsored Working Group guidelines. Of the 50 patients who were non-responders, 27 (54%) had a > or = 50% sustained reduction in the absolute lymphocyte count. The ratio of deoxycytidine kinase to cytoplasmic 5'-nucleotidase was predictive of 2-CdA responsiveness. Fourteen patients with fludarabine-failed chronic lymphocytic leukemia were also treated. No responses were achieved and 2 patients had progressive disease. Six patients had a > or = 50% reduction in the absolute lymphocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:2-Chlorodeoxyadenosine in the treatment of hairy cell leukemia and chronic lymphocytic leukemia. 790 51

The agent 2-chlorodeoxyadenosine (2-CdA) has chemotherapeutic activity in hairy cell leukemia (HCL) and in refractory chronic lymphocytic leukemia (CLL). The cytotoxic activity of 2-CdA requires the intracellular accumulation of 2-CdA nucleotides. Deoxycytidine kinase (dCK) and cytoplasmic 5'-nucleotidase (5'-NT) are the principal enzymes that phosphorylate 2-CdA and dephosphorylate 2-CdA 5'-monophosphate, respectively. The net accumulation of 2-CdA nucleotides may therefore depend on both dCK and 5'-NT. The purpose of the present experiments was to determine if there is a relationship between pretreatment levels of dCK and 5'-NT in HCL and in CLL cells, and the clinical outcome of 2-CdA treatment. As measured by a direct immunoassay for dCK in 25 CLL patients, and by a 5'-NT activity assay in 23 patients, mean dCK levels were significantly higher in 2-CdA responders than in nonresponders (P < .01), whereas mean 5'-NT levels were significantly lower in 2-CdA responders than in nonresponders (P < .05). Mean dCK levels were higher in six HCL 2-CdA responders than in one nonresponder, whereas mean 5'-NT levels were lower in the 2-CdA responders than in the nonresponder. These results suggest that both dCK and 5'-NT are determinants of 2-CdA responsiveness.
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PMID:Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. 809 16

The nucleoside analog 2-chlorodeoxyadenosine (CdA, Cladribine) is a chemotherapeutic agent for treatment of leukemias and lymphomas, most successfully used in hairy cell leukemia and B-cell chronic lymphocytic leukemia. CdA is phosphorylated intracellularly to its monophosphate derivative by the enzymes deoxycytidine kinase and deoxyguanosine kinase. Cell lines deficient in deoxycytidine kinase were shown to be resistant to CdA and a high deoxycytidine kinase level in combination with low 5'-nucleotidase has been proposed to partly explain the selectivity in CdA toxicity for lymphoid cells. In this report biochemical properties in CdA phosphorylation mediated by deoxycytidine kinase and deoxyguanosine kinase are reviewed and discussed in relation to the further metabolism of CdA 5'-monophosphate, the different possible mechanisms of action and the correlation with clinical response. It is concluded that much is known about the metabolism and mechanisms of action of CdA, but that the remarkable therapeutic effect in hairy cell leukemia has yet to be explicitly explained.
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PMID:On the phosphorylation of 2-chlorodeoxyadenosine (CdA) and its correlation with clinical response in leukemia treatment. 872 3

Bryostatin 1 (Bryo-1) has been shown to differentiate chronic lymphocytic leukemia (CLL) cells to the hairy cell leukemia phenotype. The purine analogue 2-chlorodeoxyadenosine (2-CdA) exhibits enhanced activity in patients with hairy cell leukemia compared to those with CLL. Here we present a case report of a patient diagnosed with resistant CLL and treated sequentially with Bryo-1 followed by 2-CdA for three cycles. Molecular and biochemical parameters relative to the sequential treatment with these agents in vivo were comparable to those found in the WSU-CLL cell line in vitro (R. M. Mohammad et al., Clin. Cancer Res., 4: 445-453, 1998; R. M. Mohammad et al., Biol. Chem., 379: 1253-1261, 1998). There was a significant reduction of lymphocyte count from 37.1 x 10(3)/microl before the treatment to 3.4 x 10(3)/microl after treatment, and partial remission was achieved 2 months after the treatment. The percentage of morphologically differentiated lymphocytes was increased from 3% before treatment to 92% with the first cycle of Bryo-1. Similarly, expression of CD22, a marker of differentiation, increased from 38% to 97% and was maintained at a high level for the duration of the treatment. Analysis of the molecular markers of apoptosis in isolated peripheral blood lymphocytes revealed an increase in the Bax:Bcl-2 ratio after treatment with Bryo-1 in cycles 2 and 3, with associated poly(ADP-ribose) polymerase cleavage after Bryo-1 and 2-CdA treatment. The deoxycytidine kinase: cytosolic 5'-nucleotidase activity ratio increased modestly after Bryo-1 treatment, indicating increased sensitivity of the peripheral blood lymphocytes to 2-CdA. In summary, we found that sequential treatment with Bryo-1 and 2-CdA caused a significant reduction in peripheral blood lymphocytes (CLL cells) with simultaneous induction of differentiation and the initiation of the Bax: Bcl-2 apoptotic pathway.
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PMID:Sequential treatment of a resistant chronic lymphocytic leukemia patient with bryostatin 1 followed by 2-chlorodeoxyadenosine: case report. 1077 58

Hereditary adenosine deaminase deficiency results in failure of the lymphocyte development. This occurs because of the accumulation of deoxyadenine nucleotides in cells with high deoxycytidine kinase and low 5'-nucleotidase activity. 2-Chlorodeoxyadenosine (2-CdA) resists the action of adenosine deaminase and accumulates in cells with high deoxycytidine kinase and low 5'-nucleotidase activity. It is equally toxic to dividing and nondividing cells and may act by preventing repair of DNA single-strand breaks. In doses of 0.1 mg/kg/day given for seven days 2-CdA manifests low toxicity. It has been found to be effective in the treatment of patients with lymphoid neoplasms, including advanced cutaneous T-cell lymphomas, chronic lymphocytic leukemia, non-Hodgkin lymphomas, and hairy cell leukemia. In the latter disorder it appears to be as or more effective than the tight-binding adenosine deaminase inhibitor, deoxycoformycin, and is probably less toxic. 2-CdA also appears to be effective in controlling autoimmune hemolytic anemia and shows promise in the treatment of other autoimmune diseases.
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PMID:2-Chlorodeoxyadenosine (2-CdA): A Potent Chemotherapeutic and Immunosuppressive Nucleoside. 2746 4