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 activity of asparagine synthetase decreased almost 50% during dexamethasone-induced mouse myeloid leukemia M1 cell differentiation. This enzyme activity also declined significantly during differentiation of the human myelogenous leukemic cell lines, HL-60 and U-937, induced by either macrophage culture supernatant or retinoic acid. The decline of asparagine synthetase activity closely paralleled the expression of various maturation markers, but could also be induced by serum starvation. These results suggest that asparagine synthetase or L-asparagine has some biological function in growth regulation of these leukemia cell lines.
Leukemia 1990 Oct
PMID:Decrease in asparagine synthetase activity during cell differentiation of mouse and human leukemia cell lines. 197 72

A polytropic recombinant retrovirus containing the envelope gene of Friend mink cell focus-inducing virus plus the remainder of the genome of an amphoropic murine leukemia virus was propagated on mouse embryo fibroblasts and mink lung cells. Virus particles, metabolically labeled with [2-3H]mannose, were harvested from the culture supernatants and lysed with detergents. The viral envelope glycoprotein was isolated from the lysates by immunoaffinity chromatography and purified by preparative SDS/PAGE. Oligosaccharides were liberated by sequential treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H and peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase F and fractionated by high-performance liquid chromatography. Individual glycans were characterized chromatographically, by methylation analyses and in part, by enzymic microsequencing. The results demonstrated that viral glycoproteins, synthesized in mouse embryo fibroblasts, carried as major constituents partially fucosylated diantennary, 2,4- and 2,6-branched triantennary and tetraantennary complex type N-glycans with 0-4 sialic acid residues and only small amounts of high-mannose type species with 5-9 mannose residues. As a characteristic feature, part of the complex type glycans contained additional Gal(alpha 1-3) substituents. Glycoprotein obtained from virions propagated on mink lung cells, contained partially fucosylated diantennary and 2,4-branched triantennary oligosaccharides with 1-3 sialic acid residues, in addition to trace amounts of high-mannose type species with 8 or 9 mannose residues. Thus, the results reveal that predominantly, the complex type N-glycans of the retroviral envelope glycoprotein display cell-specific variations including differences in oligosaccharide branching, sialylation and substitution by additional Gal(alpha 1-3) residues.
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PMID:Glycosylation of the envelope glycoprotein from a polytropic murine retrovirus in two different host cells. 217 68

A human histiocytic lymphoma cell line, U937, is highly sensitive to L-asparaginase with an ID50 of about 0.0001 U/ml after 72 hr of culture. When U937 cells were made resistant to either L-asparaginase (1 U/ml) or asparagine deprivation, the activity of asparagine synthetase increased to 80- or 7-fold of the wild type, respectively. The phenotype of the resistance to L-asparaginase turned out to be stable under nonselective conditions for over several months. The hybrids between L-asparaginase sensitive (Molt4) and resistant (HL-60) cell lines revealed the latter phenotype in terms of L-asparaginase sensitivity and the activity of asparagine synthetase. Furthermore, U937 cells resistant to L-asparaginase could survive in glutamine-free media with 1.5-fold elevation of glutamine synthetase activity. These results altogether clarify the role of asparagine synthetase in L-asparaginase toxicity and have a good implication for the clinical use of L-asparaginase.
Leukemia 1989 Apr
PMID:Biochemical characterization of U937 cells resistant to L-asparaginase: the role of asparagine synthetase. 256 53

The objective of this study was to investigate the antiretroviral activity of specific inhibitors of glycosidases and mannosidases that are involved in N-linked oligosaccharide processing of glycoproteins. Castanospermine and 1-deoxynojirimycin, potent inhibitors of glucosidases I and II, showed significant activity against Moloney murine leukemia virus (IC50: 1.2 microgram/ml). Deoxymannojirimycin and swainsonine, inhibitors of mannosidase I and II, respectively, did not show any activity. These observations suggest that removal of the outermost glucose residue from high mannose asparagine-linked oligosaccharide may be essential for the replication of mouse leukemia virus. The relative nontoxic nature of these inhibitors and a novel mechanism of action suggest a potential for compounds of this type as chemopreventive and therapeutic agents in the treatment of acquired immune deficiency syndrome (AIDS).
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PMID:Antiretroviral activity of castanospermine and deoxynojirimycin, specific inhibitors of glycoprotein processing. 296 Mar 21

Human hemopoietic blast colony-forming cells (BI-CFCs) recognize and adhere to the extracellular matrix (ECM) produced by marrow-derived stromal cells in vitro. We have investigated the requirements for this interaction by testing the capacity of BI-CFCs to adhere to ECM components under a variety of conditions. Binding was prevented completely by prior treatment of stromal ECM with nitrous acid, in large part by treatment with heparitinase or hyaluronidase, and slightly by treatment with chondroitinases. Whereas heparan sulfate isolated from marrow stromal cultures effectively blocked binding, heparan sulfate from bovine kidney did not. Chondroitin sulfate and hyaluronic acid did not have any effect in this test. In contrast, collagen was not sufficient for the interaction because dishes coated with collagen type I or IV did not act as adhesive surfaces for BI-CFCs. Ligands for integrin receptors (e.g., fibronectin) did not participate in BI-CFC binding because the synthetic pentapeptide glycine-arginine-glycine-asparagine-serine did not compete with stroma in binding BI-CFCs. These findings indicate that heparan sulfate in the bone marrow microenvironment is necessary for BI-CFC binding to ECM and may contribute to localizing hemopoietic stem cells in hemopoietic tissue.
Leukemia 1988 Dec
PMID:Heparan sulfate is necessary for adhesive interactions between human early hemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment. 297 4

For the purpose of clinical application to the therapy of human leukemia and lymphosarcoma, L-asparaginase from Escherichia coli was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) by an improved method, which involves a purification step of activated PEG2 by gel filtration. The PEG2-modified asparaginase retained approximately 30% (73 IU/mg of protein) of the enzymic activity of the native enzyme, while it had almost wholly lost the immunoreactivity towards anti-asparaginase antibodies. The modified enzyme retained the characteristics of the native enzyme in terms of the pH- and temperature-dependencies of activity and stability, and the Km value for L-asparagine. Administration of the modified enzyme to a dog with spontaneous lymphosarcoma induced complete remission without any toxic side effects. Seven children with multiple relapses of acute leukemia were treated with a regimen of cycles of methotrexate and native asparaginase. Three of these children developed anaphylactic shock. In contrast to the native enzyme, the successive administration of PEG2-modified asparaginase to those three patients was therapeutically effective without causing any allergic reaction.
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PMID:Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia. 310 31

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

The int-1 proto-oncogene is the first cellular gene discovered and implicated in tumorigenesis solely on the basis of repeated insertional mutations that activate transcription of the gene. The gene is silent in most tissues but expressed in the embryonic central nervous system, in the late (post-meiotic) stages of spermatogenesis, and in a high proportion of mouse mammary tumor virus-induced carcinomas, when a provirus is inserted upstream or downstream of the coding domain. The functional significance of int-1 in the oncogenic process is supported by the demonstration that murine leukemia virus-based vectors carrying the gene can alter the morphology and growth properties of an established line of mammary epithelial cells. The predicted primary protein product of the int-1 gene is 370 amino acids in length and cysteine-rich; immunoprecipitation with anti-peptide antibodies reveals multiple species of int-1 protein, due to asparagine-linked glycosylations and probable cleavage of a signal peptide. However, the active product of the gene and its biochemical behavior during normal development and mammary tumorigenesis are not known.
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PMID:The int-1 proto-oncogene. 333 19

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

Peptides recognized by rabbit antibodies to vasoactive intestinal peptide (VIP) were extracted from diisopropyl fluorophosphate-treated rat basophilic leukemia (RBL) cells and resolved by filtration on Sephadex G-25 in 50 mM acetic acid. The immunoreactive VIPs of RBL cells eluted from Sephadex G-25 at 35-41%, 53-60%, and 69-73% bed volume, but not at 63-68% as for the neuropeptide VIP1-28. The two forms of immunoreactive VIP larger than VIP1-28 reacted with antibodies to both VIP1-9 and VIP10-28, but the smallest was bound only by antibodies to VIP10-28. The smallest immunoreactive VIP was purified by ion-exchange and reverse-phase high-performance liquid chromatography, and the amino acid sequence was determined to be that of VIP10-28 with asparagine-free acid at the carboxyl terminus rather than the amide of VIP neuropeptide. Challenge of RBL cells with 1 microM ionophore A23187 at 37 degrees C released VIP10-28 rapidly to a mean of 75% at 5 min and 77% at 30 min. The VIP generated and released by mast cells thus consists of a mixture of peptides that all differ structurally from the neuropeptide VIP.
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PMID:Structurally distinctive vasoactive intestinal peptides from rat basophilic leukemia cells. 337 62


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