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)

Tumor target cells (TC) are lysed by natural killer (NK) cells provided that they (1) form conjugates with the effector cells, (2) activate effector cells to release cytotoxic factors, and (3) they are susceptible to the lytic effect of these factors. While this cascade of events that leads to TC killing has been defined, the signal molecules responsible for each of the steps remain largely undetermined. A variety of human leukemia-derived TC lines and clones were analyzed for their sensitivity to NK cell-mediated lysis and for their ability to bind and activate NK cells. These characteristics have been correlated with TC surface expression of differentiation antigens and carbohydrate residues. Of the cell lines and clones tested, K562, SPI-802, MOLT-4, MOLT-4/C8-1, ZS, KG-1/A-3, and HL-60S were sensitive to NK cell-mediated lysis, while KG-1, THP-1-0, HL-60R, and LFM were resistant. KG-1, THP-1-0, HL-60R, and LFM cells were further studied to determine mechanisms responsible for their resistance to NK cells. It was found that HL-60R and LFM cells were unable to bind NK cells. In contrast, KG-1 and THP-1-0 cells were able to bind to and activate NK cells. Therefore, it is likely that the NK-resistance of KG-1 and THP-1-0 cells may be related to their lack of sensitivity to cytotoxic factors released by bound NK cells. All of the TC cell lines and clones capable of binding NK cells expressed the 3-fucosyl-N-acetyl-lactosamine hapten (Lex or SSEA-1 antigen) recognized by the monoclonal antibody Leu M1. These TC consistently lacked surface L-fucose residues, as shown by lack of Ulex europaeus agglutinin binding. In contrast, HL-60R and LFM which did not form conjugates with NK cells, did not express surface Lex determinants and avidly bound the Ulex agglutinin. Distinct subpopulations of NK-resistant KG-1 cells expressed Lex antigens or bound Ulex. We compared KG-1/A-3, a NK-sensitive cell clone, with the parental NK-resistant KG-1 cell line. KG-1/A-3 lost the ability to bind the Ulex lectin displayed by the parental cell line and showed increased expression of Lex determinants. Results from these phenotypic analyses suggest that expression of Lex determinants and Ulex binding sites on the TC membrane are mutually exclusive and their expression or absence may correlate with mechanisms which regulate TC-NK cell interactions.
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PMID:Human leukemia-derived cell lines and clones as models for mechanistic analysis of natural killer cell-mediated cytotoxicity. 243 54

The coordinate increase in the hepatic production of the acute phase plasma proteins appears to be mediated by several cytokines produced by different cell types. One factor, hepatocyte-stimulating factor III (HSF-III), constitutively produced by human squamous carcinoma (COLO-16) cells, stimulates the synthesis of the same set of acute phase plasma proteins as the structurally distinct IL-6. The physicochemical properties of HSF-III coincide with those of the T cell-derived leukemia-inhibitory factor (LIF). Human rLIF, tested on hepatoma cells, indicated a liver-regulating activity identical to HSF-III. The LIF activity is specifically neutralized by HSF-III antibodies. COLO-16 cells contain an LIF mRNA which is characteristic for lectin-stimulated T cells, suggesting that HSF-III is an epidermal cell-derived form of LIF. This result provides additional evidence for the close relationship between acute phase regulation of the liver and control of proliferation and differentiation of hemopoietic cells by identical cytokines.
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PMID:Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. 247 20

The interactions of five different lectins: peanut (PNA), lentil (LEN), wheat germ (WGA), soybean (SBA), Asparagus pea (FBP) with leukaemic cells obtained from 31 children: 25 with acute lymphoblastic leukaemia (ALL) and 6 with acute myeloblastic leukaemia (AML) were examined in this study. The relationship of lectin-binding ability to cells cytomorphological, cytochemical and immunological features and its potential clinical application were investigated. It has been shown that PNA and LEN receptors were found in the majority of blast cells. The SBA reacting cells were found only in few patients and FBP binding was not found in studied ALL and AML cells. There was a clear difference in the WGA binding capacity in ALL cells with L1 and L2 characteristics respectively. No differences were found in PNA. WGA and LEN reactivity between PAS negative and PAS positive leukaemic cells. Only PNA of all studied lectins seemed to differentiate T- from B-ALL blast cells. Only WGA binding of ALL cells showed the positive correlation to the risk index value.
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PMID:Binding of lectins to human leukaemic cells. 247 5

A growth-inhibitory (GI) factor, that specifically inhibits the growth of mouse monocytic leukemia cells, was found in conditioned medium of mouse lung tissue, but not in that of mouse brain, heart, liver, or kidney tissue. Conditioned medium of spleen or bone marrow cells had low GI activity. Pulmonary macrophages were as active as peritoneal and bone-marrow-derived macrophages in production of the GI activity. The GI factor inhibited the growth of murine monocytic leukemia cell lines Mm-A and J774.1, but scarcely inhibited the growth of other mouse cell lines, such as a myeloblastic leukemia cell line (M1), a Friend erythroleukemia cell line (745A) and a mammary carcinoma cell line (FM3A). It had no significant effect on the growth of human monocytic leukemia cell lines U937 and THP-1 or on the HL-60 promyelocytic leukemia cell line. These results suggest that the GI factor produced by mouse lung tissue preferentially inhibits the growth of mouse monocytic cells. The GI factor was found to be a proteinaceous substance with a molecular mass of 25 kDa. On chromatofocusing, the GI activity was eluted with Polybuffer 96/acetic acid at pH 7.2-7.5. The GI activity was not significantly decreased by heat treatment at 56 degrees C for 30 min or acid treatment (0.01 M HCl, 14 h), but the GI activity in glycosidase-treated conditioned medium of lung tissue was lost on heat treatment. The GI activity could not be neutralized with anti-(interferon alpha + beta) antibody. The activity was produced constitutively by lung tissues and its production was not stimulated appreciably by lipopolysaccharide, lectin, or poly(I).poly(C). The GI factor appears to be a cytokine unrelated to known cytokines such as tumor necrosis factor, interleukin-1, transforming growth factor beta, and interferons. These results suggest that the GI factor may be involved in negative feedback regulation of macrophage production in steady-state conditions in the lungs.
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PMID:Normal mouse lung tissue produces a growth-inhibitory factor(s) preferential for mouse monocytic leukemia cells. 248 Aug 47

We investigated the expression of fos oncogene proteins in lymphoproliferative disorders, using a monoclonal antibody (FO-120) that was prepared against a synthetic oligopeptide of fos protein (amino acid sequence from 127 to 152). Although peripheral blood leukocytes were rarely positive for FO-120, they were transiently stained after lectin (PHA) stimulation. After culture with IL-2 for 1 or 2 weeks, less than 40% of the lymphocytes weakly reacted with FO-120, whereas strongly positive cells were detected in more than 70% of cells in half the T-cell lines established from preleukemic state of adult T-cell leukemia (pre-ATL) and all of ATL derived T-cell lines. All in vivo specimens of non-Hodgkin's malignant lymphomas, except for one case of T-cell lymphoma were also strongly positive. In addition, the extent of the antibody reactivity correlated with the histopathological grade of malignancy in B-cell lymphoma. The reactivity to most AILD-IBL lesions overlapped with that to T-lymphomas, and could be distinguished from that to reactive lesions. FO-120 appears to be a useful tool for detecting early neoplastic changes in lymphoproliferative disorders.
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PMID:Detection of fos oncogene products by monoclonal antibody FO-120 in lymphoproliferative disorders. 251 20

A rapid rise in the level of cytosolic free calcium ([Ca2+]i) is believed to be one of several early triggering signals in the activation of T lymphocytes by antigen. Although Ca2+ release from intracellular stores and its contribution to Ca2+ signaling in many cell types is well documented, relatively little is known regarding the role and mechanism of Ca2+ entry across the plasma membrane. We have investigated mitogen-triggered Ca2+ signaling in individual cells of the human T-leukemia-derived line, Jurkat, using fura-2 imaging and patch-clamp recording techniques. Phytohemagglutinin (PHA), a mitogenic lectin, induces repetitive [Ca2+]i oscillations in these cells peaking at micromolar levels with a period of 90-120 s. The oscillations depend critically upon Ca2+ influx across the plasma membrane, as they are rapidly terminated by removal of extracellular Ca2+, addition of Ca(2+)-channel blockers such as Ni2+ or Cd2+, or membrane depolarization. Whole-cell and perforated-patch recording methods were combined with fura-2 measurements to identify the mitogen-activated Ca2+ conductance involved in this response. A small, highly selective Ca2+ conductance becomes activated spontaneously in whole-cell recordings and in response to PHA in perforated-patch experiments. This conductance has properties consistent with a role in T-cell activation, including activation by PHA, lack of voltage-dependent gating, inhibition by Ni2+ or Cd2+, and regulation by intracellular Ca2+. Moreover, a tight temporal correlation between oscillations of Ca2+ conductance and [Ca2+]i suggests a role for the membrane Ca2+ conductance in generating [Ca2+]i oscillations in activated T cells.
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PMID:Mitogen-induced oscillations of cytosolic Ca2+ and transmembrane Ca2+ current in human leukemic T cells. 251 22

Previous studies demonstrated that activation of T lymphocytes by phorbol ester or mitogenic lectin leads to phosphorylation of Ser 126 of the CD3 antigen gamma chain, whereas treatment with ionomycin results in phosphorylation of both Ser 123 and 126 [Davies, A. A. et al. (1987) J. Biol. Chem. 262, 10918-10921]. In the present study, the dephosphorylation of Ser 123 and Ser 126 of the gamma chain was investigated. Phorbol-ester-induced phosphorylation of the gamma-chain Ser 126 in vivo was reversed following removal of phorbol ester. Dephosphorylation of both Ser 123 and 126 was also observed in vitro using the microsome fraction of T lymphocytes. In order to identify the phosphatases acting at these two sites, the immunoprecipitated gamma chain was used as substrate either following treatment with protein kinase C in vitro, in which case phosphorylation occurs mainly at Ser 123, or following in vivo phosphorylation of Ser 126. Purified oligomeric forms of the polycation-stimulated phosphatases were more effective in dephosphorylating both phosphorylated forms of the gamma chain compared with equivalent amounts of ATP,Mg2+-dependent phosphatases or calcineurin. By using phosphopeptide analogues of the CD3 gamma chain containing Ser 123 or Ser 126 as substrates (A3 and A6), it was shown that polycation-stimulated phosphatases selectively dephosphorylated Ser 123 compared to Ser 126. In order to determine which phosphatases dephosphorylate the gamma chain in microsomes, A3 and A6 were used as substrates for characterising phosphatases in microsomes from human T leukaemia Jurkat 6 cells. Three phosphopeptide phosphatases (250-400 kDa) co-eluted through five purification steps with three forms of polycation-stimulated phosphorylase phosphatase. The partially purified A3/A6 phosphopeptide phosphatases were insensitive to Ca2+, calmodulin and inhibitor-1, and dephosphorylated A3 preferentially compared with A6. A latent form of microsomal ATP,Mg2+-dependent phosphorylase phosphatase was stimulated 10-fold by trypsinisation, but did not dephosphorylate phosphopeptides A3 and A6. The results show that high-Mr forms of polycation-stimulated phosphatases are the only enzymes in human T leukaemia cell microsomes which dephosphorylate gamma chain phosphopeptides. The data point to an important role for polycation-stimulated phosphatases in regulating the phosphorylation state, and so function(s), of the CD3 antigen.
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PMID:Dephosphorylation of the human T lymphocyte CD3 antigen. 254 Sep 70

Large granular lymphocytes (LGL) have been characterized phenotypically and functionally as cytotoxic T lymphocytes, NK cells or lymphokine-activated killer cells. The most prominent morphologic feature of LGL is large cytoplasmic granules that are thought to contain the molecules responsible for cell lysis. In this study, we describe the morphologic and functional characteristics of IL-2-dependent cytotoxic lymphocytes derived from feline PBL. Stimulation of feline PBL with Con A followed by culturing in 50 U of gibbon monkey IL-2 human rIL-2 induced long term lymphocyte cultures. These lymphocytes are cytotoxic for the feline leukemia virus-induced T cell lymphoma (FL74), in a 4-h 51Cr release assay. All cell lines are either constitutively cytotoxic for FL74 cells, or cytotoxic in a lectin-dependent cell cytotoxic assay, the latter being a characteristic of low passage cultures. In contrast, no cell lines express self lysis or lysis for other lines. [3H]TdR uptake showed that 1 U of human rIL-2 produces a 50% maximal proliferative response by feline lymphocytes suggesting a high degree of homology between the ligand binding sites of feline and human IL-2R. Feline cytotoxic lymphocytes possess abundant cytoplasm containing large azurophilic granules characteristic of LGL. These granules are bound by a bilipid membrane and contain numerous smaller membrane-bound vesicles 50 to 60 nm in diameter. A model is proposed, whereby subsequent to binding of LGL to target cell the large granules fuse to the LGL plasma membrane and release the small vesicles into the binding pocket. The vesicles then transport the lytic molecules directly and selectively to the target cell membrane.
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PMID:Feline cytotoxic large granular lymphocytes induced by recombinant human IL-2. 254 49

The effects of the differentiation-inducing agents N6, O2'-dibutyryl cyclic AMP, beta-all-trans retinoic acid, dimethylsulfoxide and butyrate on the levels of galactoside-binding proteins (lectins) in cultured human and murine tumor cells were examined by immunoblotting. Differentiation was associated with decreased levels of a 34-kDa lectin in the K-1735P and B16-F1 melanoma cells and decreased levels of a 14.5-kDa lectin in S20 neuroblastoma, MDA-MB 175 breast carcinoma, HL-60 and THP-1 leukemia cells. The level of a 14.5-kDa lectin increased during differentiation of F-9 embryonal and KM12P colon carcinoma cells. These results indicate that tumor cell differentiation along specific pathways is accompanied by distinct modulation of lectin expression. These changes may recapitulate the normal developmental regulation of lectin expression.
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PMID:Modulation of galactoside-binding lectins in tumor cells by differentiation-inducing agents. 255 43

A cDNA encoding the Mac-2 antigen, a surface marker highly expressed by thioglycollate-elicited macrophages, has been cloned by immunoscreening of a lambda gt11-P388D1 expression library. The nucleotide sequence of the cDNA is identical to that of carbohydrate-binding protein 35, a galactose-specific lectin found in fibroblasts and highly homologous to a rat IgE-binding protein from basophilic leukemia cells. The in vitro synthesized Mac-2 protein displayed the expected carbohydrate- and IgE-binding properties. By pulse-chase analysis and subcellular fractionation studies, the Mac-2 protein was found in the cytosol but was also seen to accumulate in the extracellular medium. The latter finding was surprising in view of the fact that the cDNA did not encode a signal peptide or transmembrane domain. An alternatively spliced cDNA with the potential to encode a NH2 terminally extended Mac-2 protein with a stretch of hydrophobic amino acids at its NH2 terminus was also found, but it is not clear whether it is the source of the extracellular Mac-2. Possible functions for the Mac-2 protein based on its lectin- and IgE-binding properties are discussed.
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PMID:The Mac-2 antigen is a galactose-specific lectin that binds IgE. 258 31


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