Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A congenital erythrocyte pyruvate kinase (PK) deficiency was found in a 72-year old female patient with chronic myelomonocytic leukemia (CMML). Erythrocyte PK deficiency was associated with an increase in the activity of hexokinase, 6-phosphogluconate dehydrogenase and glutathione peroxidase in erythrocytes as well as a decrease in acetylcholinesterase, glutathione reductase and glucosephosphate isomerase activities. The enzymatic abnormalities were accompanied by alterations in hemoglobin and in i antigen content of erythrocyte membrane. In addition, bone marrow ultrastructural studies showed dyshemopoietic changes in all blood cell lines and especially in erythroblasts. The present findings confirm the close relationship between CMML and acquired dyserythropoietic syndromes and constitute a new observation of the infrequent association of hereditary erythrocyte enzymopathies and leukemia. A survey of the literature is presented.
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PMID:Chronic myelomonocytic leukemia associated with hereditary pyruvate kinase deficiency and multiple acquired erythrocyte abnormalities. 10 94

The catalase activities of HP50-2 and HP100-1 cells, which are H2O2-resistant cell lines derived from human leukemia HL-60 cells, were 3 and 18 times higher, respectively, than that of HL-60 cells. These catalase activities of the resistant cells were precipitated with anti-catalase serum. The glutathione peroxidase activity of HP50-2 cells was about twice that of HL-60 or HP100-1 cells. The superoxide dismutase activities of HP50-2 and HP100-1 cells were, respectively, about 4 and 2 times that of HL-60 cells. In addition, both the resistant cell lines were completely devoid of myeloperoxidase activity. Pulse-labeling experiments showed that the syntheses of catalase in HP50-2 and HP100-1 cells were, respectively, 2 and 4 times that in HL-60 cells, and that, unlike the parent cells, neither line synthesized myeloperoxidase. Thus the alteration of catalase, glutathione peroxidase, and superoxide dismutase activity could be linked to the resistance of H2O2 of human leukemia cells.
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PMID:High production of catalase in hydrogen peroxide-resistant human leukemia HL-60 cell lines. 131 86

Oxidative biotransformation of xenobiotics and endogenous substances involves glutathione in reduced form as an integral component through two mechanisms: glutathione peroxidase catalysing the reduction of hydrogen peroxide and organic hydroperoxides, and glutathione-S-transferases catalysing the conjugation of oxygenated derivatives with glutathione. We studied glutathione and glutathione-related enzyme activities in haemolysed venous blood samples from 49 healthy children and from 11 children with diabetes mellitus, 10 children with rheumatoid arthritis, seven children with active coeliac disease, and seven children with acute lymphoblastic leukaemia. Among the healthy children glutathione content and the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were unrelated to sex; age-dependent differences were also minor. The patients with diabetes mellitus had decreased activity of glutathione reductase. The patients with acute lymphoblastic leukaemia had increased activity of both glutathione peroxidase and glutathione-S-transferase, possibly reflecting an adaptive response to free-radicals. The patients with active coeliac disease had control levels of all measured parameters of glutathione-related reactions indicating, since we earlier found decreased activities of glutathione peroxidase in intestinal mucosa of celiacs, that blood may not always reflect tissue-specific changes.
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PMID:Glutathione and glutathione-metabolizing enzymes in the erythrocytes of healthy children and in children with insulin-dependent diabetes mellitus, juvenile rheumatoid arthritis, coeliac disease and acute lymphoblastic leukaemia. 204 16

The effects of catalase treatment were studied in two in vitro passaged ascites tumour lines (ATP C+ and EAT) and in three in vitro established human myeloid leukemia cell lines (HL-60; KG-1; KG-1a) characterized by the arrest of cells at different stages of maturation. The results demonstrate that catalase treatment favoured proliferation in the in vitro passaged ascites tumour cells, but not in the in vitro established leukemia lines. Enzyme assays on five in vitro cell lines revealed that catalase was only present in HL-60. Although glutathione peroxidase activity was initially found in all five cell lines, it disappeared from two ascites tumour cells when they were transferred in culture. It is hypothesized that catalase treatment favours ascites tumour cell proliferation because it replaces glutathione peroxidase in eliminating H2O2.
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PMID:Antioxidant enzymes and proliferative activity of cell lines of different origin. 261 35

An important biological function of glutathione (GSH) resides in the detoxication reactions mediated by enzymes such as glutathione-S-transferase (GSTs) and glutathione peroxidase (GPX). An increasing body of evidence implies that GSH and these enzymes play important roles in determining the sensitivity of tumours against cytotoxic drugs like quinone antibiotics, in particular adriamycin (Adr). In the present study, we have analysed the effects of cell-cycle on GSH and GSH-dependent enzymes in an attempt to explain cell-cycle specificity of these antileukaemic drugs which were shown to be involved in free-radical-type reactions. Determination of GSH, GST, GPX and superoxide dismutase in cell-cycle-enriched fractions of five different human myeloid leukaemia cell lines (KG1, K562, U937, ML-1 and ML-2) yielded results identical to those obtained in random cultures, which implies that neither GSH nor GSH-related enzymes are cell-cycle regulated. These findings argue against the presumption that cell-cycle specificity of cytotoxic drugs like Adr could be due to the glutathione-dependent metabolism in myeloid leukaemia cell lines.
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PMID:Influence of cell cycle on glutathione-S-transferase, selenium-dependent glutathione peroxidase, superoxide dismutase and glutathione levels in human myeloid leukaemia cell lines. 276 62

Mammalian erythrocytes have large amounts of catalase, an enzyme which catabolizes hydrogen peroxide (H2O2). Because catalase has a low affinity for H2O2, others have suggested that glutathione peroxidase clears most H2O2 within the erythrocyte and that catalase is of little import. We hypothesized that erythrocyte catalase might function to protect heterologous somatic cells against challenge by high levels of exogenous H2O2 (e.g., in areas of inflammation). We find that, whereas nucleated cells (L1210 murine leukemia) are readily killed by an enzymatically generated flux of superoxide (and, therefore, H2O2), the addition of human and murine erythrocytes blocks lethal damage to the target cells. Inhibition of erythrocyte superoxide dismutase, depletion of glutathione, and lysis of the erythrocytes do not diminish this protection. However, inhibition of erythrocyte catalase abrogates the protective effect and the addition of purified catalase (but not superoxide dismutase) restores it. Furthermore, erythrocytes derived from congenitally hypocatalasemic mice (in which other antioxidant systems are intact) do not protect L1210 cells. Our results raise the possibility that the erythrocyte may serve as protection against by-products of its own cargo, oxygen.
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PMID:Erythrocyte catalase. A somatic oxidant defense? 394 56

Rat basophilic leukemia cells have frequently been employed for investigating the pathways of leukotriene biosynthesis, a class of biologically active arachidonic acid metabolites. However, information is lacking on the levels of selenium-dependent glutathione peroxidase (Se-GSH-Px), non-Se-GSH-Px and glutathione S-transferases (GSH-S-Trs), key enzymes involved in fatty acid hydroperoxide metabolism and leukotriene biosynthesis in these cells. Both GSH-S-Trs and non-Se-GSH-Px reactions are catalyzed by the same enzyme. In the present studies, we have measured the enzyme activities of GSH-Px(s) and GSH-S-Trs in the 105,000 X g supernatant fraction of sonified RBL-1 cells. The specific activities for GSH-Px(s) toward H2O2, cumene hydroperoxide, and 15S-hydroperoxy-eicosatetraenoic acid (15S-HPETE) are 12.6, 17.9 and 26.9 nmoles X min-1 X mg-1 protein, respectively. A specific activity of 18.9 nmoles X min-1 X mg-1 protein with 1-chloro-2,4-dinitrobenzene was estimated for the GSH-S-Trs. Therefore, the cell fraction that exhibits 5-lipoxygenase activity also contains selenium and non-selenium glutathione peroxidases.
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PMID:Measurement of glutathione requiring enzymes involved in arachidonic acid cascade of rat basophilic leukemia cells. 644 77

The activity of enzymatic defences against free radical attack including superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione reductase have been compared in some experimental animal tumours with the corresponding normal mouse tissues. The activity of SOD in PC6 plasmacytoma and P388 lymphocytic leukaemia was lower than in normal lymphocytes and the activity in a mouse bladder carcinoma (MB) was one-half of that of the normal bladder tissue. Similarly PC6, P388, TLX5 lymphoma and MB showed lower catalase activity than the corresponding normal tissues. The activity of glutathione peroxidase in tumours was in general comparable with that of the normal tissues with the exception of MB, while TLX5, PC6 and P388 contained much lower glutathione reductase activity than normal lymphocytes. The results suggest that it may be possible to selectively destroy certain tumours by peroxidative attack, and that P388 leukaemia would be much more sensitive than L1210 leukaemia to free radical production.
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PMID:Activities of free radical metabolizing enzymes in tumours. 686 May 48

The ectoenzyme gamma glutamyltransferase (GGT) a second messenger generating enzyme activity on the cytoplasmic membrane was biochemically analyzed in leukemic cells from patients with acute lymphoblastic and myeloid leukemias. The lower mean activity--0.594 IU/mg protein was noticed in patients with acute lymphoblastic leukemias (ALL), while the higher--0.956 IU/mg protein was found in acute myeloid leukemia patients (AML) in serum and 0.151 IU/mg protein in polymorphonuclear cells. The levels of the activity of glutathione reductase (GR) were increased but the activities of glutathione peroxidase (GSH Px) were significantly decreased in serum of leukemia patients.
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PMID:Activities of enzyme transducing extracellular signals--gamma glutamyltransferase and enzymes metabolizing glutathione in acute lymphoblastic and myeloid human leukemias. 761 77

Murine leukemia L1210 cells rendered deficient in glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) by Se deprivation (L.Se(-) cells) were found to be more sensitive to tert-butyl hydroperoxide (t-BuOOH) cytotoxicity than Se-replete controls (L.Se(+) cells). Human K562 cells, which express PHGPX, but not GPX, were also more sensitive to t-BuOOH in the Se-deficient (K.Se(-)) than Se-satisfied (K.Se(+)) condition. In examining the metabolic basis for selenoperoxidase-dependent resistance, we found that glucose-replete Se(-) cells reduce t-BuOOH to t-butanol far more slowly than Se(+) cells, the ratio of the first-order rate constants approximating that of the GPX activities (L1210 cells) or PHGPX activities (K562 cells). Monitoring peroxide-induced changes in GSH and GSSG gave consistent results; e.g., glucose-depleted L.Se(+) cells exhibited a first order loss of GSH that was substantially faster than that of glucose-depleted L.Se(-) cells. Under the conditions used, peroxide-induced conversion of GSH to GSSG could be stoichiometrically reversed by resupplying D-glucose, indicating that no significant lysis or GSSG efflux and/or interchange had taken place. The apparent first-order rate constant for GSH decay increased progressively for L1210 cells expressing a range of GPX activities from approximately 5% to 100%, demonstrating that peroxide detoxification is strictly dependent on enzyme content. The initial rate of 14CO2 release from D-[1-14C]glucose supplied in the medium was much greater for L.Se(+) or K.Se(+) cells than for their respective Se(-) counterparts, consistent with greater hexose monophosphate shunt activity in the former. These results highlight the importance of selenoperoxidase action in the glutathione cycle as a means by which tumor cells cope with hydroperoxide stress.
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PMID:Selenoperoxidase-dependent glutathione cycle activity in peroxide-challenged leukemia cells. 777 66


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