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 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

Mitochondria from human acute lymphoblastic leukemia cells contain an ATP-independent DNA topoisomerase which can relax negative and positive supercoils. This enzyme has been purified 200-fold by carboxymethyl-cellulose or double stranded DNA-cellulose chromatography. In contrast to the molecular weights reported for mitochondrial topoisomerases in other systems, the native leukemia enzyme has a molecular weight of 132,000 daltons as determined by gel permeation chromatography in buffer containing 0.4 M KC1. It also exhibits a sedimentation coefficient of 7.1 S when centrifuged through a 10-30% glycerol gradient in this high salt buffer. The enzyme is presumably a type I topoisomerase analogous to those found in rat liver and Xenopus laevis mitochondria.
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PMID:Isolation of a mitochondrial DNA topoisomerase from human leukemia cells. 632 1

Autologous bone marrow transplantation is potentially curative in the treatment of acute leukemia if residual leukemic cells in the marrow can be eliminated prior to transplantation. We studied the purging effects of a synthetic alkyl-lysophospholipid (ALP) on marrow containing leukemic cells from a transplantable myelomonocytic leukemia (WEHI-3B) in BALB/c mice. Simulated remission bone marrow containing 2% leukemic cells treated in vitro with 20 and 100 micrograms/mL of ET-18-OCH3 (1-octadecyl-2-methyl-sn-glycerol-3-phosphocholine) significantly prolonged survival of lethally irradiated transplanted recipients. At a dose of 100 micrograms/mL, 88% of the mice survived for the duration of the experiment (approximately five months). Autopsies showed that 25% of these survivors had microscopic evidence of leukemia. Thus, in vitro treatment of marrow eliminated leukemic blasts and spared sufficient normal stem cells to allow hematologic reconstitution. The effect of ET-18-OCH3 is not entirely selective for leukemic cells. A spleen colony assay showed that ALP has some cytotoxic effect on normal hematopoietic stem cells.
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PMID:Purging murine leukemic marrow with alkyl-lysophospholipids. 638 66

A glyceride derivative of chlorambucil (2), 1,3-dipalmitoyl-2-[4-[bis (2-chloroethyl)amino]benzenebutanoyl]glycerol (1), was synthesized and tested as an orally administrable antineoplastic drug endowed with lymphotropic properties. A significantly higher efficacy (increased life span) and a reduced toxicity of 1, relative to 2, were apparent when both compounds given per os were evaluated against P388 leukemia subcutaneously implanted in mice, a situation where the tumor cells disseminate along the lymphatic route. In order to assess the selective absorption of 1 by the intestinal lymphatic system after oral administration, we determined plasma and intestinal lymphatic concentrations and compared them with that obtained with 2. The results clearly demonstrate that the esterification of 2 to a diacylglycerol moiety brings about considerably higher levels in the lymph and reduces plasma levels. Moreover, pharmacokinetic and biological data suggest that 1 is most probably acting by itself rather than as a prodrug of chlorambucil.
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PMID:1,3-dipalmitoylglycerol ester of chlorambucil as a lymphotropic, orally administrable antineoplastic agent. 687 88

Two to five units of platelet concentrate were frozen together in single bags using glycerol-glucose as cryoprotective agents and a special freezing plate which produced a reproducible, rapid freezing rate when immersed in liquid nitrogen. After thawing there was no loss in platelets compared to prefreezing controls. Phase microscopic evaluation after thawing, however, demonstrated large numbers of severely damaged platelets and a significant decrease in morphology score. Total ATP levels fell to 37-52% of controls, and thawed platelets did not aggregate with adenosine diphosphate or collagen or undergo release of nucleotides following incubation with thrombin. In vivo recovery one hour after transfusion of autologous platelets administered to patients with leukemia was significantly inferior (p less than 0.025) to results achieved in the same patients with autologous platelets frozen with dimethylsulfoxide. These results indicate that significant damage occurs following freezing and thawing utilizing glycerol-glucose as cryoprotective agents for frozen platelets and that further investigation is required prior to their clinical use. Blood banks currently interested in platelet cryopreservation for clinical use should utilize dimethylsulfoxide as a cryoprotective agent.
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PMID:Cryopreservation of platelet concentrates using glycerol-glucose. 707 14

An aberrantly expressed and highly active abl tyrosine kinase (p210bcr-abl) appears critical for the development and pathogenesis of chronic myelogenous-leukemia (CML). CML cells and cell lines each displayed a similar spectrum of phosphotyrosyl proteins. Analysis of these proteins by glycerol-gradient ultracentrifugation showed that many apparently existed as multimeric complexes. Confirming this, several of these proteins co-immunoprecipitated, along with the p210bcr-abl, with antibody to abl. Included were co-precipitating proteins identified as the p120 ras GTPase-activating protein (GAP) and the p62 protein that binds both to GAP and to a number of other tyrosine-phosphorylated proteins having peptide regions homologous to the second domain of src. Because p62, ras GAP and ras are involved in growth-factor and oncogene activation of cells, this pathway may also play an important role in CML.
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PMID:Tyrosine phosphorylated proteins in chronic myelogenous leukemia. 750 42

The effect of serum on the antineoplastic action of the alkyl-lysophospholipid 1-octadecyl-2-O-methyl-sn-glycerol-3-phosphocholine (ET-18-OCH3) was studied in two human leukemia cell lines, HL60 and K562, and in leukemic cells of patients. Decreasing amounts of serum in the culture medium enhanced the cytotoxic action of ET-18-OCH3 dramatically in both cell lines and in the leukemic cells, as measured by cell survival and proliferation. Uptake of ET-18-OCH3 was likewise increased at reduced serum levels. Similar effects were obtained when fetal calf serum (FCS) in the culture medium was substituted by bovine serum albumin (BSA, fatty acid free). Selectivity of the alkyl-lysophospholipid at reduced serum or BSA level was demonstrated by clonogenic assays of normal marrow progenitor cells. Our study provides an optimalization of the purging conditions in autologous bone marrow transplantation, by using a low concentration of BSA during ET-18-OCH3 treatment (20 micrograms/ml for 4 h) in serum-free culture medium.
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PMID:Influence of serum levels on leukemic cell destruction by the ether lipid ET-18-OCH3. 759 55

5'-Phosphatidyl-5-fluorouridines, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by 5-fluorouridine, were designed to be potent antitumor agents. 5'-Phosphatidyl-5-fluorouridines with a variety of diacyl or dialkyl residues in the glycerol moiety, were synthesized by phospholipase D-catalyzed transphosphatidylation from the corresponding phosphatidylcholine and 5-fluorouridine. These new compounds were evaluated in mice with experimental tumors by ip and po administration. Dipalmitoyl and distearoyl derivatives 1b and 1c had the greatest antitumor activity against both P388 leukemia and Meth A fibrosarcoma in mice.
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PMID:Nucleosides and nucleotides--CXXXVII. Antitumor phospholipids with 5-fluorouridine as a cytotoxic polar-head: synthesis of 5'-phosphatidyl-5-fluorouridines by phospholipase D-catalyzed transphosphatidylation. 760 85

Cross-linking of the immunoglobulin E receptor on rat basophilic leukemia (RBL)1 cells by multivalent antigen activates phosphatidylinositol (PI) kinase and phosphatidylinositol 4-phosphate (PIP) kinase leading to the increased production of PIP and phosphatidylinositol 4,5-bisphosphate (PIP2). Activators of protein kinase C (PKC), such as phorbol myristate acetate (PMA) and the synthetic diacylglycerol, 1,2-dioctanoyl-sn-glycerol (diC8), were found to have the same effect even though PMA and diC8 do not cause the activation of phospholipase C. Although the kinetics are different depending on the stimulant, activation of PKC using multivalent antigen, PMA or diC8 also causes the polymerization of actin and an increase in the F-actin content of the cells. In all cases, a good correlation was observed between F-actin levels, activation of PI and PIP kinases, and the increased production of PIP and PIP2. However, in the case of antigen, there is no correlation between actin polymerization and the total amount of PIP and PIP2. Staurosporine, an inhibitor of protein kinases, blocks the F-actin response and the increased synthesis of PIP and PIP2 with similar dose dependencies. Furthermore, depletion of PKC activity through long-term exposure to PMA, inhibited both the F-actin response and the increased synthesis of PIP and PIP2 induced by either DNP-BSA or diC8. These results suggest that activation of PKC precedes the activation of PI and PIP kinases and that under certain circumstances activation of the kinases and the increased synthesis of PIP and PIP2 may be involved in the polymerization of actin in RBL cells, possibly through the interaction of the polyphosphoinositides with actin-binding proteins such as gelsolin and profilin.
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PMID:Activation of protein kinase C in rat basophilic leukemia cells stimulates increased production of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: correlation with actin polymerization. 774 99

Retroviral DNA integration requires the activity of at least one viral protein, the integrase (IN) protein. We cloned and expressed the integrase gene of feline immunodeficiency virus (FIV) in Escherichia coli as a fusion to the malE gene and purified the IN fusion protein by affinity chromatography. The protein is active in site-specific cleavage of the viral DNA ends, DNA strand transfer, and disintegration. FIV IN has a relaxed viral DNA substrate requirement: it cleaves and integrates FIV DNA termini, human immunodeficiency virus DNA ends, and Moloney murine leukemia virus DNA ends with high efficiencies. In the cleavage reaction, IN exposes a specific phosphodiester bond near the viral DNA end to nucleophilic attack. In vitro, either H2O, glycerol, or the 3' OH group of the viral DNA terminus can serve as nucleophile in this reaction. We found that FIV IN preferentially uses the 3' OH ends of the viral DNA as nucleophile, whereas HIV IN protein preferentially uses H2O and glycerol as nucleophiles.
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PMID:Activities of the feline immunodeficiency virus integrase protein produced in Escherichia coli. 810 10


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