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)

Feline leukemia virus contains a protease which apparently has the same specificity as murine leukemia virus protease. It cleaves in vitro the Pr65gag of Gazdar-mouse sarcoma virus into the constituent p15, p12, p30, and p10 proteins. We purified the protease and determined its NH2-terminal amino acid sequence (the first 15 residues). Alignment of this amino acid sequence with the nucleotide sequence (I. Laprevotte, A. Hampe, C. H. Sherr, and F. Galibert, J. Virol. 50:884-894, 1984) reveals that the protease is a viral-coded enzyme and is located at the 5' end of the pol gene. As previously found for murine leukemia virus (Y. Yoshinaka, I. Katoh, T. D. Copeland, and S. Oroszlan, Proc. Natl. Acad. Sci. U.S.A. 82:1618-1622, 1985), feline leukemia virus protease is synthesized through in-frame suppression of the gag amber termination codon by insertion of a glutamine in the fifth position, and the first four amino acids are derived from the gag gene.
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PMID:Translational readthrough of an amber termination codon during synthesis of feline leukemia virus protease. 299 7

A 12.4 kbp HindIII chromosomal DNA fragment harbouring an apparently intact 9.2 kbp endogenous murine leukaemia virus (MuLV)-related proviral genome was isolated from an RFM/Un strain mouse by molecular cloning and designated pRFM #6. Nucleotide sequence analysis revealed the following characteristic features in the pRFM #6 provirus: a distinct 200 bp sequence in the long terminal repeat (LTR) mid-U3 region, a primer binding site for glutamine tRNA, a 3' pol region encoding an 'endonuclease' protein of 390 amino acids, and the mink cell focus-forming virus type-specific sequence at the 5' portion of the env gene. The 699 bp 5' LTR and 700 bp 3' LTR of pRFM #6 provirus were identical except for three base changes in the U3 'enhancer' region. At the cell-provirus DNA junction, 4 bp direct repeats were present. The proviral genome was found at the same chromosomal DNA site in BALB/c, AKR, C3H, CBA and RFM strain mice, but not in NFS/N or C57BL/6 strain mice.
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PMID:Characterization of a molecular clone of RFM/Un mouse chromosomal DNA that contains a full-length endogenous murine leukaemia virus-related proviral genome. 302 98

The transport of L-threonine and L-glutamine into murine P388 leukemia cells has been characterized. Threonine appears to be a specific substrate for a Na+-dependent amino acid transport system similar to system ASC of the HTC hepatoma cell. Threonine transport is uninhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid and alpha-(methylamino)isobutyric acid, shows a pattern of transport similar to that seen in HTC hepatoma cells over the pH range of 5.5-7.5, and is inhibited by L-serine and L-cysteine. Approximately two-thirds of glutamine transport into P388 cells also appears to enter P388 cells via this ASC-analogous system. However, based upon (a) inhibition studies with threonine (where the K1 of threonine inhibition of glutamine transport was 7-fold the Km of threonine transport), (b) inhibition analysis of glutamine transport with various amino acids and amino acid analogues, and (c) different patterns of transport between threonine and glutamine over the pH range of 5.5-7.5, approximately one-third of glutamine transport can be attributed to a second Na+-dependent amino acid transport system. This system appears to be similar to the system N of rat hepatocytes. Glutamine and threonine do not appear to enter P388 cells via systems A or L to any significant degree. P388 cells do not appear to exhibit 'adaptive regulation' of amino acid transport. Differences in 'adaptive regulation' could therefore not be utilized for comparing threonine and glutamine transport.
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PMID:Characterization of L-threonine and L-glutamine transport in murine P388 leukemia cells in vitro. Presence of an N-like amino acid transport system. 308 65

Several side-effects of asparaginase therapy have been said to be a consequence of the glutaminase activity of Escherichia coli asparaginase, especially the deleterious influence on the liver function. We report here the drug-induced impairments of asparagine and glutamine metabolism in correlation to concentrations changes of plasma proteins, synthesized in the liver, in patients with acute lymphatic leukaemia. One hour after asparaginase application, plasma glutamine decreased to 5% (0-39%: median, range) of the initial values, with a subsequent rise to concentrations slightly lower than those prior to therapy. During the 14 days of drug application the fasting plasma concentrations of glutamine fell to a median of 63% of the pre-therapeutic levels, indicating a depletion of the glutamine pools. Two days after the end of asparaginase application, in one patient the glutamine concentrations increased to the pre-therapeutic range. Plasma concentrations of fibrinogen and antithrombin III decreased to 46% and 56%, respectively, of the initial values, with a slight increase 2 days after the end of therapy. The changes of plasma protein concentrations followed the course of plasma glutamine and asparagine. From that we deduce that the hepatic synthesis of the plasma proteins might be influenced by asparagine and glutamine depletion as a consequence of the therapy with E. coli asparaginase.
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PMID:Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects. 314 4

An endogenous retroviruslike DNA, B-26, was cloned from a BALB/c mouse embryo gene library by using a generalized murine leukemia virus DNA probe. Southern blot hybridization and nucleotide sequence analyses indicated that B-26 DNA might be a novel member of the GLN DNA family (A. Itin and E. Keshet, J. Virol. 59:301-307, 1986) which contains murine leukemia virus-related pol and env sequences. Northern analysis indicated that B-26-related RNAs of 8.4 and 3.0 kilobases were transcribed in thymus, spleen, brain, and liver tissues of 6-week-old BALB/c mice.
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PMID:Structure, distribution, and expression of an ancient murine endogenous retroviruslike DNA family. 317 46

HTLV-IIIB-infected H9 cells are shown to contain a high level of the natural UAG suppressor glutamine tRNA(UmUG Gln); this tRNA has been demonstrated to be required for the synthesis of Moloney murine leukemia virus (Mo-MuLV)-encoded protease. After cultivation of HTLV-IIIB-infected H9 cells with Avarol at a concentration (1 microgram/ml), previously found to protect the cells against the cytopathic effects of HTLV-III, an almost complete inhibition of the synthesis of the tRNA(UmUG Gln) was observed. Moreover, we obtained some evidence that the processing of the HTLV-III precursor protein p53 to p24 is inhibited by Avarol in infected cells, suggesting that the compound interferes with the expression of the viral protease gene.
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PMID:Inhibition of expression of natural UAG suppressor glutamine tRNA in HIV-infected human H9 cells in vitro by Avarol. 320 12

The uptake system for 6-diazo-5-oxo-L-norleucine (DON) was studied in mouse P388 leukemia cells. The DON transport system was found to resemble that of another glutamine antimetabolite, Acivicin, in its strong temperature dependence, utilization of the "L" transport system, inhibition by glutamine but not by glutamate, potent inhibition by p-chloromercuribenzene sulfonate, Na+, and only minimal inhibition by various energy poisons. A Km of approximately 70 microM and a Vmax of 3.4 nmoles/10(6) cells/min was calculated for this cell line. The accumulated DON was not metabolized by P388 cells and moderate efflux occurred at 37 degrees C. The DON transport characteristics of a DON-resistant P388 cell line (100 times ID50 of parent line) were similar to those of the DON-sensitive parent line, indicating that altered drug transport may not be involved in development of resistance to this antimetabolite. The finding that an Acivicin-resistant subline of P388 cells which exhibited good transport of DON showed negligible transport of Acivicin suggests different modes of resistance towards the two glutamine antimetabolites.
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PMID:Uptake of glutamine antimetabolites 6-diazo-5-oxo-L-norleucine (DON) and acivicin in sensitive and resistant tumor cell lines. 336 93

A rapid, reproducible HPLC method based on dansyl chloride derivatization has been developed for the determination of L-asparagine, L-aspartate, L-glutamine, and L-glutamate in mouse and human serum samples. This improved procedure has been designed for automation with an autoinjector system. Studies with mice bearing the sensitive and the asparaginase-resistant L5178Y leukemia show that this analytical method can be employed to monitor the effect of L-asparaginase on serum levels of these four amino acids. The method can be used to monitor serum amino acid levels in patients undergoing therapy with L-asparaginase.
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PMID:Serum amino acid levels in leukemic mice after L-asparaginase treatment. 337 8

The mixed disulfide of methyl mercaptan and L-homocysteine, S-(methylthio)-L-homocysteine (L-SMETH), inhibits the growth of L-1210 leukemia cells in culture at micromolar concentrations. The inhibition is markedly promoted by added cupric ion, but not by ions of other metals, is stereospecific, and is competitive with glutamine. For example, at 10 microM each of L-SMETH and Cu2+, almost complete growth inhibition was observed if cells were grown in 1 mM glutamine, 50% inhibition at 2 mM glutamine, and none at 4 mM glutamine. The inhibition is also completely relieved by cytidine in noncompetitive manner, but not by guanosine or uridine, indicating that the principal damage to the cellular economy resides in the amination of UTP to CTP. This was confirmed by high performance liquid chromatography analysis of cell extracts, which showed a marked decrease in CTP with increases in the levels of UTP, GTP, and ATP. A major swelling of cells leading to lysis accompanies the inhibition and increases in DNA and protein per cell confirms this unbalanced growth. The chemical basis for this biological interaction is presented.
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PMID:Evidence for a copper:S-(methylthio)-L-homocysteine complex as a glutamine antagonist of cytidine triphosphate synthesis in L1210 murine leukemia cells. 341 27

It has been found that leukemia cells can be induced by various agents [e.g., by retinoic acid (RA)] to mature to a nonproliferative end stage. It has also been found that normal mature granulocytes produce a chalone-like "hemoregulatory peptide (HP)" which seems to be involved in the inhibitory proliferation control of myelopoietic cells. In view of the intended use of maturation induction treatment as an alternative to current antileukemic therapy it appeared to be of interest to know if granulocytes, obtained by RA treatment of the promyelocytic leukemia cell line HL-60, would produce normal HP or if their transformed phenotype would cause production of deviant regulatory peptide(s). It was found that conditioned media from RA-treated HL-60 cells inhibited myeloid proliferation but strongly stimulated the growth of erythroid and lymphoid cells. A low molecular weight thiol-containing peptide was isolated which inhibited colony formation by normal granulocyte-macrophage committed stem cells but unlike HP had no effect on (untreated) HL-60 cells themselves. It was also shown that the HL-60 RA peptide is chemically different from HP in terms of molecular size, electrophoretic mobility, composition, and NH2-terminal sequence, which was determined as glutamine-aspartic acid-proline. It is concluded that differentiated HL-60 cells produce hemoregulatory factor(s) with properties different from those of normal HP. The implication of a possible abnormal regulatory behavior of induced leukemic populations is discussed with respect to leukemia therapy by differentiation induction.
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PMID:Identification of a regulatory peptide distinct from normal granulocyte-derived hemoregulatory peptide produced by human promyelocytic HL-60 leukemia cells after differentiation induction with retinoic acid. 346 Jun 96


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