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)

The number of specific (3H)ouabain binding sites and dissociation constants (Kd) were determined by Scatchard analysis of values for leucocytes from patients with B-cell chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), acute blastic leukaemia (AL) and healthy subjects. CLL lymphocytes and normal B-cells bound significantly less (3H)ouabain than did normal T-lymphocytes. CML granulocytes showed the same binding characteristics as normal granulocytes, while blast cells from AL patients bound significantly more (3H)ouabain than did normal granulocytes or B-cells. The increased binding capacity in blast cells might, at least partly, reflect their larger cell size. A decrease in Kd values was only found in CLL lymphocytes, as compared with normal B-cells. Intralymphocytic sodium content in CLL lymphocytes was significantly increased, as compared with that in T-cell-enriched normal lymphocytes. (3H)ouabain binding did not show any relationship to different prognostic variables in CLL. The present data mainly argue against altered Na+/K+-ATPase enzyme activity as an indicator of malignancy.
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PMID:(3H)ouabain binding to leukaemic cells and intralymphocytic sodium content in chronic lymphocytic leukaemia; no evidence for alterations of the Na+/K+-pump. 303 63

Incubation of L1210 murine leukemia cells in vitro with 10 microM of the bifunctional alkylating agent bis(2-chloroethyl)methylamine (nitrogen mustard, HN2) for 10 min brought about a fall of more than 99.9% in their ability to form colonies when the cells were suspended in 0.5% nutrient agar. Incubation with HN2 also inhibited the influx of the potassium congener 86Rb+ to exponentially proliferating L1210 cells in a concentration-dependent manner. This inhibition was specific and was accounted for by a reduction of a diuretic-sensitive component of 86Rb+ influx, identified in the preceding paper (Wilcock, C. and Hickman, J.A. (1988) Biochim. Biophys. Acta 946, 359-367) as being mediated by a Na+/K+/Cl- cotransporter. Inhibition by 10 microM HN2 was complete after a 3-h incubation. There was no inhibition at this time of the ouabain-sensitive component of 86Rb+ influx, mediated by Na+/K+-ATPase. After 3 h of incubation with 10 microM HN2 there was also no change in the membrane potential of the treated cells as measured by the distribution of the [3H]TPMP+, no decrease in cellular ATP concentration and no change in intracellular pH, and the ability of the cells to exclude the vital dye Trypan blue was not significantly different from control values. These effects of HN2, therefore, appeared to follow lethal damage, but precede cell death. In the stationary phase of L1210 cell growth, the component of HN2 and diuretic-sensitive K+ influx to L1210 cells was reduced, whilst the component constituting the HN2-insensitive ouabain-sensitive sodium pump was increased. The monofunctional alkylating agent MeHN1 (2-chloroethyldimethylamine) which cannot cross-link cellular targets and has no antitumor activity, did not inhibit 86Rb+ influx to L1210 cells when incubated at equimolar or equitoxic concentrations to HN2. Intracellular potassium concentration was maintained close to control values of 138 +/- 10 mM in HN2-treated cells because of an approx. 35% fall in cell volume. The results suggest that the Na+/K+/Cl- cotransporter is a selectively inhibitable target for HN2, and the lesion is discussed with reference to the cytotoxic effects of this agent.
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PMID:Selective inhibition by bis(2-chloroethyl)methylamine (nitrogen mustard) of the Na+/K+/Cl- cotransporter of murine L1210 leukemia cells. 320 52

After cyclophosphamide priming, subcutaneously (s.c.) transplanted cells from established human leukemia cell lines U937, K562, or HL-60 consistently yielded single, nonmetastatic tumors. Tumorigenesis with KG-1 cells was inconstant. Within each cell line, cytologic, electron-microscopic, cytogenetic, isoenzyme, immunochemical, and enzyme cytochemical studies confirmed identity of cultured and tumor cells. Adenosine triphosphatase reactivity was limited to leukemic cells in vivo. Isoenzyme electrophoretic patterns, distinct for each cell line, provided a reliable criterion to establish clonality and to verify tumor cell origin. Antitumor activity of the active vitamin-D3 metabolite 1,25-(OH)2D3 was assessed in vivo against U937, K562, and HL-60 cells by cell transplantation and concurrent s.c. contralateral implantation of miniosmotic pumps containing the 1,25-(OH)2D3 in a propylene glycol vehicle. Tumors developed in all treated U937 mice, 50% with K562 and 25% bearing HL-60 transplants. All transplants proliferated in mice either with pumps containing only vehicle or no pumps. Coincidence of tumor and vehicle decreased survival time. No differences in cytoreactivities or morphology were apparent between cultured cells and tumor cells in treated or untreated mice. This nude mouse system is useful for in vivo studies of human myelogenous leukemia cells. Implanted miniosmotic pumps provide controlled delivery of antineoplastic agents and their vehicles for in vivo studies. 1,25-(OH)2D3 may be a valuable adjunctive therapeutic for control of human myelogenous leukemias.
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PMID:Action of 1,25-(OH)2D3 in nude mice bearing transplantable human myelogenous leukemic cell lines. 386 96

It is shown that cholesterol incorporation into the membranes of Zajdel hepatoma cells, lymphoblast leukemia cells L1210 and into those of ovary tumour causes an increase in the membrane phospholipid bilayer microviscosity measured by pyrene as fluorescent probe. The increase in the membrane lipid microviscosity resulted in a decrease in the activity of Na,K-ATPase and 5-nucleotidase of the tumour cells. After the injection of tumour cells with an increase of cholesterol/phospholipid ratio we observed an increase of the life-span of experimental animals as compared to the control groups.
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PMID:[Changes in the microviscosity of lipid bilayer membranes of various malignant cells and tumor transplantability]. 395 87

Deoxythymidine-5'-triphosphatase (dTTPase) from human serum was separated by DEAE-cellulose chromatography from unspecific hydrolases in a single step. The method was adapted to a microscale and the enzymatic activity was determined for five different groups of patients including epithelial carcinoma, leukemia and three control groups. The result is that the purified dTTPase preparations of these groups reflect the situation obtained in the whole serum.
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PMID:A one-step liquid-chromatographic technique for the estimation of the deoxythymidine-5'-triphosphatase in human serum. 609 26

Using electron microscope cytochemistry and cells separated on Ficoll-Hypaque, Mg2+-dependent ATPase, ADPase and 5'-nucleotidase were predominantly localized as ectoenzymes on normal human granulocytes. Large deposits of ATPase final reaction product and more finely granular deposits of 5'-nucleotidase final reaction product were firmly attached to the outer surface of cell plasma membranes. The final reaction product from ecto-ADPase was, however, only loosely associated with the plasma membrane. In addition, finer deposits of ADPase final reaction product were seen in specific granules and in background cytoplasm. No nucleotidase phosphatase activity was localized to the alkaline phosphatase-containing granules (phosphasomes) recently described by Rustin et al. In granulocytes from patients with chronic granulocytic leukaemia, ecto-ATPase had a patchy distribution on the plasma membranes. There was considerable heterogeneity between cells with regard to ADPase and 5'-nucleotidase localization. In some cells, ADPase was seen only at both site, while in some cells no activity was detected. 5'-Nucleotidase localization was normal in some cells but lacking from many. No correlation was found between enzyme heterogeneity and the degree of morphological cell maturity.
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PMID:Electron microscopic cytochemical localization of nucleoside phosphatases in normal and chronic granulocytic leukaemic human neutrophils. 611 13

Myosin purified from a murine myeloid leukaemia cell line (M1) that had been incubated with [32P]orthophosphate incorporated 32P into the heavy, but not the light, chain. When the heavy chain was dephosphorylated by bacterial alkaline phosphatase, myosin that had low actin-activated ATPase activity gained higher activity only in the presence of the light-chain kinase. In the absence of the light-chain kinase, however, the Mg2+-stimulated ATPase activity of myosin was not activated by actin, regardless of phosphatase treatment. These results indicate that the activity of M1 myosin ATPase is regulated by phosphorylation of both the light and heavy chains. A scheme for this regulation by phosphorylation is presented and discussed.
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PMID:Phosphorylation of the myosin heavy chain. Its effect on actin-activated Mg2+-stimulated ATPase in leukaemic myeloblasts. 613 30

The Mn2+-dependent endonuclease activity associated with the avian myeloblastosis virus RNA-directed DNA polymerase has been shown to be activated by ATP in the presence of Mg2+. In the presence of Mn2+ the endonucleolytic activity was stimulated about 3-fold by the addition of ATP. The earlier identified Mr = 40,000 Friend murine leukemia virus (F-MuLV)-associated endonuclease which functions in the presence of both Mg2+ and Mn2+ has also been shown to be similarly stimulated by ATP. For both endonuclease activities stimulation was only observed at ATP concentrations above 0.5 mM, and it did not increase upon elevating the ATP concentration above 2.5 mM. ADP and dATP also stimulated both activities, although not to the same extent as ATP. GTP had no apparent effect and AMP seemed to inhibit both activities. The effect ATP analogs had on the F-MuLV associated endonuclease activity could suggest that the endonuclease reaction in the presence of ATP might involve the cleavage of beta-gamma phosphate bonds in ATP. Neither adenyl-5'-yl imidodiphosphate nor (beta, gamma-methylene)adenosine 5'-triphosphate stimulated the activity, whereas significant stimulation was observed in the presence of (alpha, beta-methylene)adenosine 5'-triphosphate. Although no ATPase activity could be detected in the purified F-MuLV endonuclease preparation, the data do not exclude the possibility that ATP may be cleaved in amounts which are equivalent to the number of nicks introduced into DNA by the virus-associated endonuclease. In the presence of ATP and Mg2+ the F-MuLV-associated endonuclease nicked both supercoiled and linear DNA duplexes extensively, although the former was nicked more readily than the latter. Single-stranded DNA functioned poorly as a substrate. The nicks introduced by the enzyme contained a 5'-phosphoryl terminus and a 3'-hydroxyl group.
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PMID:Effect of ATP on the Friend Murine leukemia virus-associated endonuclease activity and the endonuclease activity of the avian myeloblastosis virus RNA-directed DNA polymerase. 616 71

The p30 antigen from Rauscher leukemia virus (R-MuLV) was separated into two fractions by chromatography on either phosphocellulose or DEAE-cellulose. The p30-I and p30-II were indistinguishable immunologically or by isoelectrofocusing and gel electrophoresis. An ATPase activity was tightly associated with p30-II that could not be separated by ion-exchange chromatography, isoelectrofocusing, or glycerol velocity gradient sedimentation. The ATPase hydrolyzed the gamma phosphate from only ATP or dATP. Immunoglobulin directed against R-MuLV p30 completely inhibited the p30-II associated ATPase. Glycerol velocity gradient analysis showed that p30-I sedimented as a 30-kDa species while the p30-II and its associated ATPase sedimented as a 60-kDa species. The p30-II was converted entirely to a 30-kDa form by treatment with 0.2% (w/v) lithium dodecyl sulfate, suggesting that it represented a complexed species of p30. Finally, p30-II was found to stimulate the activity of R-MuLV reverse transcriptase, but p30-I had no effect on the activity of the enzyme. These results suggested the existence of at least two different forms of p30 in R-MuLV.
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PMID:Characterization of a p30 fraction from Rauscher leukemia virus which has an associated ATPase activity. 620 91

Skin fibroblasts from patients with a variety of hematologic disorders were infected with SV40 virus in vitro in attempts to discover the reason for increased susceptibility of Fanconi anemia cells to this transforming virus. The proportion of skin fibroblasts expressing SV40 T-antigen by immunofluorescent methods was elevated in 12 patients with Fanconi anemia and in seven of nine obligate heterozygous relatives. Elevated expression was also observed in three patients with other hematological disorders at high risk of acute non-lymphocytic leukemia, but was not apparent in seven sporadic aplastic anemia patients or four of their relatives. T-antigen expression was elevated in about one-half of patients with thrombocytopenia-absent radius syndrome and related conditions, with familial aplastic anemia, and in their normal relatives. In the conditions under study, elevated T-antigen expression seemed clearly correlated with predisposition to leukemia, which may be genetically determined, but it was not associated with cytogenetic or anemic manifestations.
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PMID:Relationship of SV40 T-antigen expression in vitro to disorders of bone marrow function. 625 20


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