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)

Six cases of chronic granulocytic leukaemia (CGL) and two cases of acute myeloid leukaemia (AML) with dual populations of karyotypically normal and Philadelphia (Ph1) chromosome-positive cells are described. GTG and QF-banding characterized the Ph1 as resulting from a 9/22 translocation in all eight cases. Four of the patients suffering from CGL presented with 100% Ph1-positive bone marrows, and after receiving intensive chemotherapy, karyotypically normal cells were demonstrated. The other two patients with CGL showed Ph1 mosaicism at presentation. The two patients with AML exhibited Ph1 mosaicism at presentation and throughout the course of the disease. In both of these patients, a marker No. 10 chromosome was found in some of the Ph1-positive cells and in one hyperdiploidy was observed to have developed only in the clone with the additional chromosome anomaly.
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PMID:The significance of Ph1 mosaicism: a report of six cases of chronic granulocytic leukaemia and two cases of acute myeloid leukaemia. 29 38

A density cut method was used to prepare two subpopulations of bone marrow cells which were enriched (BE) and depleted (BD) respectively of blast cells. Marrow aspirates were obtained from 32 patients, 26 of whom had acute leukaemia. The uptake of a variety of chemotherapeutic agents by these two subpopulations and the acid-soluble ribonucleotide profiles of the populations were compared and significant differences were found in drug uptake by BE and BD subpopulations. For some drugs such as cytosine arabinoside, uptake was greatest by the BE cells, while for 5-azacytidine the BD subpopulation took up the greatest amount of the drug. The preparation of the BE subpopulation also permitted the recognition of several patients with acute leukaemia whose blast cells possess nondetectable levels of ATP, UTP, and GTP components in their acid-soluble fractions. The studies presented demonstrate the necessity of using purified cell populations when characterizing the drug uptake patterns and the soluble ribonucleotide profiles of the leukaemic cells. A simple method for enriching bone marrow aspirates for leukaemic cells is also presented.
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PMID:Drug uptake and ribonucleotide profiles of blast-enriched and blast-depleted human bone marrow cell populations. 60 55

The amount of free purine and pyrimidine ribonucleotides in the spleens of mice (C57Bl and DBA/2) and in lympholeukemia cells (La and L1210), sensitive and with induced resistance to 5-fluorouracil, was determined by chromatography on a column with DEAE-cellulose. It was found that the cytidine ribonucleotide pool in the spleens of DBA/2 mice is 2 times lower as compared to C57Bl mice. The lympholeukemia cells (La and L1210) isolated from the animals also differed in their uridine nucleotide pools. The development of leukemia was accompanied by a decrease in ATP and GTP. No significant changes in the total amount of pyrimidine nucleotides under developing resistance to 5-fluororuacil were observed.
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PMID:[Comparison of free ribonucleotide pool in the spleens of C57BL and DBA/2 mice and in leukemia cells sensitive and resistant to 5-fluorouracil]. 62 43

Agonist binding to guanine nucleotide-binding protein (G protein)-coupled receptors in membranes of myeloid differentiated human leukemia (HL-60) cells is inhibited by guanine nucleotides, most potently by the GTP analog guanosine 5'-(gamma-thio)triphosphate (GTP gamma S). In order to study whether GTP gamma S formed locally from adenosine 5'-(gamma-thio)triphosphate (ATP gamma S) and GDP by nucleoside diphosphokinase has any advantage over exogenously added GTP gamma S in binding to and activating G proteins, regulation of complement component 5a (C5a) binding to its receptors, as well as formation of GTP gamma S, was studied in membranes of HL-60 cells. GTP gamma S added to HL-60 membranes potently inhibited binding of 125I-C5a (IC50 about 3 nM), an effect not influenced by addition of either GDP or ATP gamma S. When HL-60 membranes were incubated with the combination of ATP gamma S and GDP, a marked potentiation (up to 300-fold) of the inhibition caused by either GDP or ATP gamma S alone was observed. By measuring nucleoside diphosphokinase-catalyzed formation of GTP gamma S and inhibition of 125I-C5a binding in the presence of GDP and ATP gamma S under identical assay conditions, it was found that formed GTP gamma S inhibited binding of 125I-C5a with an IC50 value of about 0.3 nM, thus being about 10-fold more potent than exogenously added GTP gamma S. These data suggest that the GTP gamma S-forming nucleoside diphosphokinase is closely associated with the C5a receptor-G protein complex and channels the formed GTP gamma S into the G protein.
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PMID:Evidence for nucleoside diphosphokinase-dependent channeling of guanosine 5'-(gamma-thio)triphosphate to guanine nucleotide-binding proteins. 133 59

Tiazofurin (TR), an inhibitor of IMP dehydrogenase, causes remissions and induced differentiation in human leukemia through lowering the concentrations of GTP and dGTP. A deoxycytidine analog, difluorodeoxycytidine (DFDC), is an anti-tumor agent phosphorylated by deoxycytidine kinase, resulting in decreased concentration of dCTP, leading to inhibition of DNA synthesis. In HL-60 cells DFDC induced differentiation and inhibited proliferation in a dose-dependent manner (IC50 = 4 nM); TR provided synergism with DFDC. DFDC inhibited proliferation in OVCAR-5 human ovarian carcinoma cells (IC50 = 25 nM) and colony formation in PANC-1 human pancreatic carcinoma cells (IC50 = 2 nM) and rat hepatoma 3924A cells (IC50 = 22 nM). TR and DFDC are synergistically cytotoxic in hepatoma cells and additive in PANC-1 cells. The two drugs together should be helpful in treating leukemias and solid tumors in humans.
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PMID:Synergistic action of tiazofurin and difluorodeoxycytidine on differentiation and cytotoxicity. 134 74

While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.
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PMID:Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein. 135 46

The role of cytosolic and membrane-associated phosphatases in regulating dephosphorylation of the CD3 antigen gamma-chain has been investigated using streptolysin-O-permeabilized T lymphoblasts and Jurkat T leukaemia cells. Permeabilization of T cells caused a rapid extrusion of cytosolic type 2A phosphatases, but a membrane-associated phosphorylase phosphatase activity remained inside the cells. This activity had the properties characteristic of type 2A phosphatases, being resistant to inhibition by type 1 phosphatase inhibitors, though it was inhibited in a time-dependent manner by ATP or by non-hydrolysable ATP analogues, but not by GTP, CTP, ITP or PPi. The membrane-associated type 2A phosphatase in permeabilized cells did not dephosphorylate the CD3 antigen gamma-chain, suggesting that cytosolic phosphatases dephosphorylate the gamma-chain in situ. Cross-linking the CD2 and CD3 antigens with a bivalent monoclonal antibody in the absence of cytosolic phosphatases induced marked phosphorylation of the CD3 gamma-chain, immunoprecipitated using a novel gamma-chain peptide analogue directed antiserum (TG1). Phosphorylation was inhibited by a protein kinase C (PKC) pseudosubstrate inhibitor, indicating that CD2/CD3-induced gamma-chain phosphorylation is a PKC-mediated event. Activation of T cells either with phorbol 12,13-dibutyrate or by CD2-CD3 cross-linking caused [32P]Pi incorporation into the same gamma-chain Ser residues. The site-mapping data suggested that PKC in situ may incorporate phosphate at the CD3 gamma-chain Ser-123 and Ser-126 residues, but that phosphate is rapidly lost from Ser-123 by cytosolic phosphatase action. Our findings underline the importance of the dual actions of kinases and phosphatases as potential regulators of T cell antigen-receptor complex function.
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PMID:CD3 and CD2 antigen-mediated CD3 gamma-chain phosphorylation in permeabilized human T cells. Regulation by cytosolic phosphatases. 135 83

Rat basophilic leukaemia cells, like mast cells from which they are derived, have surface Fc epsilon receptors that trigger secretion of inflammatory mediators when crosslinked. Both GTP-binding proteins and a rise in cytosolic calcium concentration ([Ca2+]i) are implicated in the secretory mechanism. Here we use a video-imaging technique to report that transient rises in [Ca2+]i initiated in an individual cell can spread from cell to cell in a wave-like pattern by means of a secreted intermediate, in the absence of gap-junctional communication. We find that the leukaemia cells, peritoneal mast cells and mucosal mast cells have cell-surface P2-type purinergic receptors that can trigger similar [Ca2+]i transients. We provide evidence that ATP is rapidly released, and that it can amplify [Ca2+]i signals and initial secretory responses during antigen-stimulation of rat basophilic leukaemia cells.
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PMID:Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells. 138 46

Lovastatin blocks the biosynthesis of the isoprenoid precursor, mevalonate. When Friend murine erythroleukemia (MEL) cells are cultured in medium containing lovastatin, the precursor of murine leukemia virus envelope glycoprotein (gPr90env) fails to undergo proteolytic processing, which normally occurs in the Golgi complex. Consequently, newly synthesized envelope proteins are not incorporated into viral particles that are shed into the culture medium. gPr90env appears to be localized in a pre-Golgi membrane compartment, based on its enrichment in subcellular fractions containing NADPH-cytochrome c reductase activity and the sensitivity of its carbohydrate chains to digestion with endoglycosidase H. Arrest of gPr90env processing occurs at concentrations of lovastatin that are not cytostatic, and the effect of the inhibitor is prevented by addition of mevalonate to the medium. The low molecular mass GTP-binding proteins, rab1p and rab6p, which are believed to function in early steps of the exocytic pathway, are normally modified posttranslationally by geranylgeranyl isoprenoids. However, in MEL cells treated with 1 microM lovastatin, nonisoprenylated forms of these proteins accumulate in the cytosol prior to arrest of gPr90env processing. These observations suggest that lovastatin may prevent viral envelope precursors from reaching the Golgi compartment by blocking the isoprenylation of rab proteins required for ER to Golgi transport.
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PMID:Isoprenoid requirement for intracellular transport and processing of murine leukemia virus envelope protein. 142 16

Differentiated human leukemia (HL 60) cells contain high numbers of receptors for the chemotactic factors, N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) and complement component 5a (C5a), both coupled to pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). Agonist activation of either receptor stimulated binding of the GTP analog, guanosine 5'-[gamma-thio]triphosphate (GTP[S]), to membrane G proteins and by a similar extent in a non-additive manner. The possible interaction of the two receptors was studied by measuring agonist binding to one receptor in the presence of the other receptor agonist. fMet-Leu-Phe and C5a had no effects on [125I]C5a and fMet-Leu-[3H]Phe receptor binding, respectively, when studied in the absence of regulatory ligands. Similarly, the inhibitory effects of NaCl and GDP on agonist receptor binding were not altered in the presence of the other receptor agonist. In contrast, in the presence of the GTP analogs, GTP[S] and guanosine 5'-[beta,gamma-imino] triphosphate, fMet-Leu-Phe and C5a reduced the binding of [125I]C5a and fMet-Leu-[3H]Phe, respectively, in a concentration-dependent manner. The potencies of the GTP analogs to inhibit binding of [125I]C5a and fMet-Leu-[3H]Phe was increased about 3-fold by fMet-Leu-Phe and C5a, respectively. The data presented suggest that fMet-Leu-Phe and C5a receptors share the same G protein pool in membranes of HL 60 cells and that activation of these G proteins by one of the two receptors decreases the availability of G proteins for the other receptor.
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PMID:G protein-mediated receptor-receptor interaction: studies with chemotactic receptors in membranes of human leukemia (HL 60) cells. 147 Feb 18


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