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)

We performed an immunohistochemical analysis of frozen sections from testicular biopsies from 23 children with acute lymphoblastic leukemia. Eleven cases were infiltrated by leukemia. Tumor cells were immunostained by a panel of antibodies that identified CD10, CD43, CD19, CD3, CD7, and MHC class I and II. The immunoreactivity of normal testicular components was also studied. Normal testis showed no CD10 reactivity. Wide variation in the number of stromal macrophages identified by CD11c was found. Transferrin receptor (CD71) was expressed by some stromal macrophages, by seminiferous tubules, and by Leydig cells. B lymphocytes were absent from the testicular stroma but small numbers of T lymphocytes were consistently present. MHC class I and II were expressed by most stromal cells but not by seminiferous tubules.
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PMID:An immunohistochemical study of testicular biopsies in childhood acute lymphoblastic leukemia: reactivity of normal testicular components and leukemic infiltrates. 128 64

The role of autoimmune mechanisms in the pathogenesis of retrovirus-induced leukemia was studied using as models different forms of Rauscher leukemia virus (RV) infection in mice of different strains. It was found that mice undergoing progressive course of leukemia ("progressors") produce (a) autoantibodies to a series of antigens intimately involved on immune response regulation (class II MHC antigens, cell surface markers of helper and suppressor T-lymphocytes and erythrocaryocytes, receptors for IL-2, etc.); (b) antiidiotypic antibodies which suppress both antiviral responses and autoimmune reactions against class I MHC antigens. Passive transfer of these antibodies into genetically resistant mice prior to RV inoculation breaks their resistance. Completely resistant C57BL/6 mice and mice undergoing "spontaneous" regression of leukemia ("regressors") were found to be genetically capable of (a) suppressing autoimmune reactions of "progressors" type by active synthesis of antiidiotypic antibodies; (b) producing autoantibodies to MHC class I antigens. Immunization with monoclonals to H-2Db as well as with "anti-autoimmune" antiidiotypes prior to RV infection leads to abrogation of appropriate immune reactions and development of leukemia in C57BL/6 mice.
Leukemia 1992
PMID:Autoimmunity and counter-autoimmunity in the mechanisms of retrovirus-induced leukemogenesis. 131 69

Human melanoma cells are sensitive to the lytic activity of natural killer (NK) and lymphokine-activated killer (LAK) cells in vitro. The events resulting in tumour cell killing by lymphocytic effectors have not been completely clarified, and the same target cell determinants regulating responsiveness to immune cytolysis have not yet been identified. Indeed, changes in the differentiative status of leukemia cells as well as in the expression of major histocompatibility complex (MHC) antigens have been described to modulate sensitivity to cytotoxic effectors; moreover surface expression of adhesion factors or extracellular matrix proteins by the cancer cells can promote the activation of the cytolytic effectors and has been described to correlate with tumour cell sensitivity to cytolytic cells. We reasoned that treatment with differentiation inducers could modulate melanoma cell sensitivity to NK and LAK cells. The present study demonstrates that human melanoma GLL-19 cells, when treated with the phorbol diester phorbol 12-myristate 13-acetate (PMA) in vitro, undergo growth inhibition and neuron-like differentiation. Moreover, PMA treatment induces an evident inhibition of GLL-19 cell sensitivity to NK- and LAK-mediated cytotoxicity. GLL-19 cells express constitutively MHC class I antigens. PMA treatment, however, does not modify the expression of MHC class I and class II DR antigens in human melanoma GLL-19 cells. We have finally evaluated the effects of PMA on the expression at the cell surface of adhesion factors such as ICAM-1, and extracellular matrix proteins such as collagen IV, laminin and fibronectin; we have also studied the expression of the integrin vitronectin receptor, a membrane receptor for adhesive proteins. While adhesion factors and extracellular matrix proteins appear to play an important role in the interaction between immune effector and tumour target, it can be supposed that the modulation of such membrane-associated proteins or glycoproteins induces NK and LAK resistance in cancer cells. We indeed found that PMA treatment induced in GLL-19 a marked reduction of membrane expression of collagen IV and ICAM-1; moreover PMA reduced the cell membrane expression of the integrin vitronectin receptor. On the other hand, membrane expression of fibronectin and laminin was not affected by PMA. These data indicate that the acquisition of a NK- and LAK-resistant phenotype by GLL-19 cells occurs together with cell differentiation, down-regulation of membrane expression of collagen IV, ICAM-1 and vitronectin receptor, but in the absence of changes in MHC antigens.
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PMID:Phorbol 12-myristate 13-acetate induces resistance of human melanoma cells to natural-killer- and lymphokine-activated-killer-mediated cytotoxicity. 137 27

To identify the cellular receptors and other cell surface molecules playing essential roles in the transmission of human T-cell leukemia virus type 1 (HTLV-1), we have been isolating monoclonal antibodies (mAbs) that are capable of inhibiting HTLV-1-induced syncytium formation. In the present study, we isolated two mAbs, H11 (IgM) and H14 (IgG1), inhibitory to syncytium formation in the coculture of TOM-1 or C91/PL (both HTLV-1-positive human T-cell lines) and MOLT-4/8 (HTLV-1-negative human T-cell line) by immunizing the membrane fraction of human osteosarcoma line HOS. By immunoprecipitation and immunoblotting, H11 and H14 were found to be specific for MHC class I heavy chain and beta 2-microglobulin (beta 2 M), respectively. Among the four commercially obtained mAbs, two mAbs for MHC class I antigen and two mAbs to beta 2 M, one mAb to MHC class I antigen and one mAb to beta 2 M were also found to be inhibitory to the syncytium formation. The functional comparison of these mAbs revealed that the syncytium-inhibitory mAbs induced strong homotypic cell adhesion particularly in the HTLV-1-positive T-cell lines. This cell adhesion was dependent on temperature, energy metabolism, and microfilament function but not on the activity of protein kinase C or divalent cations. These results suggest a novel type of LFA-1-independent cell adhesion induced by signal transduction via MHC class I antigen.
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PMID:Induction of strong homotypic adhesion in human T cell lines positive with human T-cell leukemia virus type 1 by monoclonal antibodies to MHC class I and beta 2-microglobulin. 138 Aug 95

The aim of this study was to determine what factors induce major histocompatibility complex (MHC) molecules on the mouse small intestinal epithelium by using immunohistochemical methods. In germ-free mice, although MHC class I molecules such as H-2K and thymus leukemia antigen (TLa) were expressed on the small intestinal epithelium, class II molecules were absent. The introduction of microorganisms into germ-free mice induced characteristic MHC molecules on the small intestinal epithelial cells. The I-A molecule was induced on the villus tip and crypt epithelial cells 7 days after conventionalization, and the I-E molecule was induced on the mid villus and crypt epithelial cells 14 days after conventionalization. The staining intensity of the H-2K molecules was increased 4 days after conventionalization. In contrast, TLa did not change during conventionalization of germ-free mice. These results suggest that the expression of MHC molecules, except for the TLa, is greatly dependent on the presence of intestinal microorganisms.
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PMID:Differential induction of major histocompatibility complex molecules on mouse intestine by bacterial colonization. 145 71

Human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia and also a neurological disease, tropical spastic paraparesis. Tax protein (p40tax) of HTLV-1 activates in trans its own transcriptional enhancer in the long terminal repeat and also those in some cellular genes such as interleukin 2 receptor alpha, granulocyte-macrophage colony-stimulating factor, Fos, Jun and MHC class I. Thus, Tax has been proposed to play a critical role in the pathogenesis induced by HTLV-1 infection. Here, we report formation of a complex of Tax protein with the precursor protein p105 of the NF-kappa B p50 subunit. p105 was co-immunoprecipitated with Tax protein from cells infected with HTLV-1 from cells transfected with the Tax expression plasmid, but not from cells transfected with inactive mutants of Tax. Furthermore, a GST-p105 fusion protein produced in Escherichia coli bound to Tax protein. These results strongly suggest that the trans-activator Tax protein forms a complex with precursor NF-kappa B p105 and plays a role in trans-activation of transcriptional initiation.
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PMID:Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105. 150 85

Resistance to radiation leukemia virus-induced leukemia is mediated by gene(s) in the H-2D region of the MHC; a clear correlation exists between disease resistance and increased H-2Dd expression on the thymocyte surface. We have investigated the molecular basis for this stimulation of H-2Dd class I expression. Elevated H-2 mRNA and H-2 transcription are demonstrated in the infected thymocytes as compared to normal thymocytes indicating that the elevation of H-2 surface expression is the result of transcriptional activation. Gel mobility assays performed with nuclear extracts of normal and infected thymocytes and sequences 5' of the H-2Dd gene show that specific binding occurs with both extracts; the binding differs both quantitatively and qualitatively, however. DNase I protection analysis detects a protein binding site that is protected only by extracts from infected cells. The protected region contains a sequence similar to the AP-1 consensus sequence. Gel shift competition assays and UV photo-cross-linking to an oligonucleotide containing this sequence demonstrate that specific binding of an H-2 binding factor 1 occurs and that this factor is not the AP-1 binding complex. This novel binding factor, activated in vivo, might also be involved in the normal regulation of H-2 gene expression by recognizing the highly conserved binding sequence (TGACGCG) found in the 5' flanking region of many MHC class I genes. This is the first demonstration of the parallel stimulation of a DNA binding activity and increased transcription occurring in thymocytes after infection with a leukemogenic retrovirus.
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PMID:A novel DNA binding activity is elevated in thymocytes expressing high levels of H-2Dd after radiation leukemia virus infection. 163 76

Recombinant interferon alpha enhanced the MHC class I antigen density on human leukaemia/lymphoma cell lines REH, U-937 and HL-60, as measured by immunocytofluorometry using specific monoclonal antibodies. A similar effect was induced (as demonstrated in REH cells), also by human leukocyte interferon-alpha. The latter, however, caused no major alterations in the expression of leukocyte common antigen (ICA; CD45) and transferrin receptor (CD71) in the cell lines examined. In REH cells, there was no interferon-induced alteration of CD10 antigen (CALLA), which in this cell line is markedly down-regulated by 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A decrease of CD4 antigen density on the cell membrane was induced by interferon-alpha in monoblastoid U-937 cells. No induction of MHC class I and II antigens by interferon-alpha was found in K-562 cell subline.
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PMID:Interferon alpha-induced modulation of leukocyte cell surface antigens: immunocytofluorometric study with human leukaemia/lymphoma cell lines. 168 18

Three predominantly CD8+ CTL lines, TIL 501, TIL 620, and TIL 660, were generated from three HLA-A2+ melanoma patients by culturing tumor-infiltrating lymphocytes in 1000 U/ml IL-2. These tumor-infiltrating lymphocytes lysed 12 of 18 HLA-A2+ autologous and allogeneic melanomas, but none of 20 HLA-A2-negative melanomas. They also did not lyse the MHC class I negative lymphoma-leukemia cell lines, Daudi, K562, or HLA-A2+ non-melanoma cell lines including PHA or Con A-induced lymphoblast, fibroblast, EBV-transformed B cell, Burkitt's B cell lymphoma, and colon cancer cell lines. Autologous and allogeneic melanoma lysis was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag among melanoma cell lines in a TCR-dependent, HLA-A2-restricted manner. Six HLA-A2-negative melanoma cell lines obtained from five HLA-A2-negative patients were co-transfected with the HLA-A2.1 gene and pSV2neo. All 17 cloned transfectants expressing cell surface HLA-A2 molecules, but none of 12 transfectants lacking HLA-A2 expression, were lysed by these three HLA-A2-restricted, melanoma-specific CTL. Lysis of the HLA-A2+ transfectants was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag on transfectants in a TCR-dependent, HLA-A2-restricted manner. These results identify the HLA-A2.1 molecule as an Ag-presenting molecule for melanoma Ag. They also suggest that common melanoma Ag are expressed among melanoma patients regardless of HLA type. These findings have implications for the development of melanoma vaccines that would induce antitumor T cell responses.
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PMID:Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. 172 79

Numerous examples of altered expression of MHC class I antigens by cells with a malignant phenotype have been described. Of particular interest in this regard has been the description of neoplastic cells with attenuated class I antigen expression. The model system used in this laboratory for understanding the molecular mediators and events associated with attenuation in MHC class I gene expression enlists the use of Abelson virus transformed leukemia cells from which H-2 surface null variants have been immunoselected. For these variants, interdiction in MHC antigen expression occurs at many levels of eukaryotic gene regulation. The regulated expression of H-2 antigens from these somatic cell variants is discussed in relationship to the mechanisms of attenuated MHC class I gene expression described for other leukemias.
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PMID:Molecular mediators and events associated with attenuated MHC class I gene expression. 177 45


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