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

The existence of a sarcoma derived from the antigen-presenting follicular dendritic cells (FDCs) has been assumed but never confirmed. This report describes a tumor from axillary lymph nodes of a 39-year-old male in which the morphologic, enzyme histochemical, and immune phenotypic data are consistent with the malignant cells being of FDC origin. Morphologically, the tumor showed a tendency toward bi- and polynucleation with areas of storiform growth pattern, resulting in an initial diagnosis of malignant fibrous histiocytoma. However, the tumor cells had interconnections with well-developed desmosomes. Enzyme histochemistry revealed strong 5'-nucleotidase activity. Immunohistologic analysis showed that tumor cells expressed two of three FDC-specific antigens (Ki-M4, BU-10, and R4/23) strongly. Virtually all myelomonocytic markers were absent. Like normal FDCs, the leukocyte antigens CD35, CD19, CD21, and CD23 were expressed strongly and CD4 antigen weakly. No staining was evident for CD45 antigen, and no nonhemopoietic cell markers were expressed. The origin of the normal FDC is obscure. Given some evidence suggesting a bone marrow origin for the FDC, this cell may represent a lineage distinct from other known cell lineages derived from bone marrow stem cells since its immune phenotype differs considerably from them.
Leukemia 1987 Jul
PMID:Immunophenotypic analysis of neoplastic cells in follicular dendritic cell sarcoma. 331 45

Vincristine sensitive (L1210) and resistant (L1210/VCR) L1210 mouse leukemia cells were studied from morphological and histochemical point of view. The morphological and histochemical findings reflected differences in membrane structure and in physiological state of sensitive and resistant cells. Numerous villous projections and cytoplasmic protrusions of the cell surface as well as higher activity of membrane enzymes (5'-nucleotidase, ATPase, alkaline phosphatase) were found in vincristine resistant cells. It is assumed that in resistant cells these differences are connected with overexpression of membrane P-glycoprotein. Moreover, in resistant cells more condensed mitochondria were found after their exposure to vincristine. This finding can reflect a higher activity of these organelles in conditions when activity of P-glycoprotein is manifested and is in agreement with increased rate of oxygen consumption by resistant cells from 2.5 +/- 0.3 to 3.3 +/- 0.2 microliter/min.10(6) cells induced by vincristine.
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PMID:Characterization of morphological and histochemical changes induced by overexpression of P-glycoprotein in mouse leukemic cell line L1210. 791 60

The relative levels of the deoxycytidine kinase (dCK), deoxyguanosine kinase (dGK), and the 5'-nucleotidase (5'-NT) are of importance for the effect of many nucleoside analogues used in the treatment of hematological malignancies. To elucidate dCK, dGK and 5'-NT gene expressions in cell lines and in samples from patients with leukemia, we have established a real-time quantitative PCR (RQ-PCR) method. From the available dCK, dGK and 5'-NT cDNA sequences we designed specific primers and fluorogenic probes for the respective genes. The mRNA of dCK, dGK and 5'-NT was also measured by semi-quantitative RT-PCR, the enzyme activities by a radioactive substrate-based technique and Western blot was used to measure the amount of dCK and dGK protein. A MOLT-4 wild-type and its 9-beta-D-arabinofuranosylguanine (Ara-G)-resistant subline was used for the methods comparisons and the RQ-PCR assay was used in 35 samples from pediatric patients with ALL and AML. The results from RQ-PCR for the cell lines were in agreement with the semi-quantitative RT-PCR. The mRNA expression for dCK, dGK and 5'-NT (expressed as the ratio of the respective gene and the reference gene) in pediatric ALL and AML patients showed a large interindividual variability from 0.06 to 2.34, non-detectable to 0.06 and 0.04 to 0.30, respectively. These results show that the quantitative evaluation by RQ-PCR is a valuable tool in the determination of dCK, dGK and 5'-NT mRNA levels in cell lines and in clinical samples which were expressed at various levels. This rapid, convenient and specific method is suitable for further studies of these genes in clinical samples.
Leukemia 2002 Mar
PMID:Real-time quantitative PCR assays for deoxycytidine kinase, deoxyguanosine kinase and 5'-nucleotidase mRNA measurement in cell lines and in patients with leukemia. 1189 43