UMLS:C0023418 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that strong epitopes recognized by anti-Friend virus (FV) cytotoxic T lymphocytes (CTL) in H-2b mice are encoded in both the env and gag/pol regions of the helper friend leukemia virus genome. Two approaches have been used to identify these epitopes. At the nucleic acid level, we have constructed env genes with either of two in-frame deletions: pKR2, an env gene with a 681-bp deletion in the gp70 region and inserted into the pSV2-gpt-1 expression vector; and pKR1, an env gene with an 81-bp deletion in the p15E region and inserted into pSV2-gpt-1. Cell clones were established by transfecting Fisher rat embryo cells with pDb (the H-2Db restriction element), pNEO (for G418 selection) and either pKR1 or pKR2. Db and env gene expression was monitored by immunoprecipitation with polyclonal antibodies or by detection of viral RNA on Northern blots. Expressor cell clones were tested for susceptibility to lysis by polyclonal anti-FV/Db CTL in 51Cr-release assays. Whereas cells expressing pKR1 were lysed to the same extent as cells expressing the intact env gene, cells expressing pKR2 were resistant to lysis, suggesting that all detectable env epitopes are encoded within the 681-bp deletion. Polypeptides representing the two most likely candidate epitopes encoded in this segment were synthesized and tested for their abilities to sensitize FRE cells expressing Db alone for lysis by the CTL. One 17-mer polypeptide, AGTGDRLLNLVQGAYQA [corrected], functioned as a strong CTL epitope in this assay, but the other 18-mer polypeptide was inactive. Studies of the role of this epitope in the immune response to candidate viral vaccines are in progress.
...
PMID:Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. 170 62

The monoclonal antibody termed SN10 (IgG1-k) which was generated and characterized in the present study shows a highly selective reactivity with fresh (uncultured) human leukemia-lymphoma cells. The antigen defined by SN10 is a cell surface glycoprotein composed of a single polypeptide chain of Mr 36,000 and designated as gp36. The primary reactivity of SN10 is against mature B-lineage leukemia-lymphoma cells. For instance, SN10 reacted with all of the 17 B non-Hodgkin's lymphoma specimens, all of the 15 B chronic lymphocytic leukemia specimens, both of the 2 B prolymphocytic leukemia specimens, all of the 3 B hairy cell leukemia specimens, and 2 of the 3 B acute lymphoblastic leukemia specimens tested. Of normal peripheral blood cells, only a marginal reactivity of SN10 was detected with a minor subpopulation (less than 1-4% among different specimens) of isolated B-cells from healthy donors. No significant reactivity of SN10 was detected against any other isolated normal peripheral blood cells which include T-cells, granulocytes, monocytes, erythrocytes, and platelets. Furthermore, no significant reactivity of SN10 was detected against normal bone marrow specimens. In immunohistological studies using frozen tissue sections, SN10 reacted well with malignant lymphomas and showed varying patterns of reaction with hyperplastic reactive lymph nodes. Various normal human tissues tested were unreactive with SN10. In general, glycoprotein 36 was more abundantly expressed on fresh (uncultured) leukemia-lymphoma cells than on cultured leukemia-lymphoma cell lines. No significant amount of circulating SN10 antigen was detected in the plasma of leukemia-lymphoma patients or normal healthy donors. Scatchard plot analysis of direct binding of radiolabeled SN10 to a fresh (uncultured) B non-Hodgkin's lymphoma cell specimen, a fresh B chronic lymphocytic leukemia cell specimen, and DND-39 (an American Burkitt's lymphoma cell line) showed equilibrium constants of 5.2, 5.8, and 6.8 x 10(8) liters/mol, respectively. Thus, SN10 shows a high binding avidity to each of the 3 B leukemia-lymphoma cell specimens tested. Ricin A chain conjugate of SN10 killed leukemia-lymphoma cells effectively, whereas the same conjugate showed no cytotoxicity against control cells. Thus, SN10 bound to target antigen on the cell surface was effectively internalized into the cell. The present results suggest the potential of SN10 for therapy as well as for diagnosis of various forms of leukemia-lymphoma, particularly mature B-lineage leukemia-lymphoma.
...
PMID:Monoclonal antibody SN10 which shows a highly selective reactivity with human B leukemia-lymphoma and is effectively internalized into cells. 170 87

The cellular gene c-abl is the normal homologue of the transforming gene (v-abl) within the genome of the Abelson leukaemia virus. The cDNA sequence coding for the cellular form of the murine abl gene (c-abl type IV) has been inserted into the baculovirus transfer vector, pAc36C, so that the c-abl gene is under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda cells infected with the recombinant transfer vector in the presence of wild type AcNPV DNA yielded recombinant, polyhedrin negative virus that expressed moderate levels of the c-Abl protein (representing approx. 0.5-1% of the stained cellular proteins as determined by densitometric scanning). The insect derived c-Abl protein was compared to the P210-BCR/ABL protein from K562 cells, a cell line derived from a patient with chronic myelogenous leukaemia. Antibodies raised against synthetic peptides based on c-abl encoded peptides react with the insect derived c-Abl. In addition, the baculovirus derived c-Abl protein has a tyrosine kinase activity as demonstrated by phosphorylation of a synthetic polypeptide and also by autophosphorylation. Phosphoamino acid analysis of immunoprecipitated, autophosphorylated baculovirus derived c-Abl protein indicates that the majority of label incorporated is on the tyrosine residues. Immunofluorescence microscopy has been used to show that the majority of the c-Abl protein expressed in cells infected with recombinant virus is located in the nuclear and plasma membranes.
...
PMID:Expression of the mouse c-abl type IV proto-oncogene product in the insect cell baculovirus system. 173 71

The mitogenic membrane glycoprotein (gp55) encoded by Friend erythroleukemia virus is inefficiently processed from the rough endoplasmic reticulum (RER) and only 3-5% reaches plasma membranes. Because this processed component (gp55P) contains larger and more complex oligosaccharides, it can be separated from RER gp55. In nonreducing conditions, gp55P is a unique disulfide-bonded dimer, whereas RER gp55 consists of monomers and dimers with diverse intrachain and interchain disulfide bonds. This suggests that gp55 folds heterogeneously and that only one homodimer is competent for export from the RER. Pulse-chase analyses of gp55 components labeled with radioactive amino acids indicated that formation of diverse disulfide-bonded components occurred within minutes of polypeptide synthesis and that malfolded components did not later isomerize to generate dimers competent for export from the RER. Chemical studies suggested that all 12 cysteines of gp55 were oxidized within 5 min after synthesis of the protein. In contrast, the envelope glycoprotein precursor (gPr90) encoded by a replication-competent murine leukemia virus folds more homogeneously, and it is then processed and cleaved to form an extracellular glycoprotein gp70 plus a transmembrane protein p15E. The fully processed glycoprotein contains an unoxidized cysteine sulfhydryl that isomerizes reversibly with a disulfide bond that links gp70 to p15E. Consequently, only a proportion of gp70 and p15E is disulfide-bonded, and dissociation occurs when the environment becomes even slightly reducing. The gp55 glycoprotein appears to be an extreme example of protein malfolding associated with imprecise and irreversible disulfide bonding. We discuss evidence that folding inefficiencies are common for retroviral proteins that have newly evolving pathogenic functions.
...
PMID:Disulfide bonding controls the processing of retroviral envelope glycoproteins. 174 94

Recent evidence indicates that the transmembrane form of IgM on murine and human B lymphocytes is physically associated with at least two proteins, forming a disulfide-linked dimer, which may control cell surface expression of IgM and also play a role in signal transduction after Ag binding (by analogy with the TCR-associated CD3 components in T lymphocytes). We have used mAb and polyclonal antibodies against an intracytoplasmic epitope on one of these polypeptides (previously identified in murine B cells as the product of the B cell specific mb-1 gene) to study the distribution of the IgM-associated dimer in human cells. By immunocytochemical staining of normal and neoplastic B cells, we show that the human mb-1 protein appears early in B cell differentiation, probably before expression of cytoplasmic mu-chain, and persists until the plasma cell stage, where it is seen as an intracytoplasmic component. According to immunohistologic analysis of reactive lymphoid tissue and lymphoma samples, mb-1 protein is completely B cell specific. Anti-mb-1 also labels B cell areas in tissues from seven different mammalian species. Finally, the Ig-associated dimer could be isolated from human hairy-cell leukemia cells in high purity and yield by affinity chromatography using anti-mb-1 antibody. Mice immunized with this material have produced a strong polyclonal response, so that it should now be possible to prepare a panel of new mAb reactive with different epitopes on both mb-1 and on its associated polypeptide(s).
...
PMID:The IgM-associated protein mb-1 as a marker of normal and neoplastic B cells. 174 62

A full-length cDNA clone has been isolated from a cDNA library prepared from mRNA of adriamycin-resistant human leukemia HL60 cells. The nucleotide sequence of this cDNA has been determined and the protein coded for by the gene identified. The cDNA encodes a polypeptide of 125 amino acids (aa) with a deduced Mr of 13750. The deduced aa sequence of this protein has 56% homology to yeast ribosomal protein S31. Western-blot analysis using antibodies directed against a synthetic peptide based on the deduced aa sequence identifies the gene product as the human ribosomal protein S25.
...
PMID:Cloning and sequencing a cDNA encoding human ribosomal protein S25. 174 3

Leukosialin, also called CD43 or sialophorin, is a major sialoglycoprotein expressed widely in various leukocytes (granulocytes, monocytes/macrophages and T-lymphocytes). Leukosialin is heavily glycosylated by O-linked oligosaccharides (70-80 oligosaccharides/molecule) and the structures of those O-glycans are characteristic to each cell lineage and differentiation stage. In particular, the branched hexasaccharide, NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6)GalNAc is specifically expressed in activated T-lymphocytes as well as in thymocytes and T-lymphocytes from patients with leukaemia, and immuno-deficiency syndromes. A portion of these O-glycans are attached to a domain with tandem repeats in the polypeptide of leukosialin. However, the entire translation product, including such tandem repeats, is coded by one exon and a short novel promoter sequence confers the expression of the leukosialin gene. Leukosialin is apparently involved in T-cell-B-cell interaction during immune reaction and binds to ligands on antigen-presenting B-cells. These results imply that leukosialin plays critical roles in immune cell interaction and differences in attached O-glycans most likely influence the interaction of leukosialin with ligands.
...
PMID:Leukosialin, a major O-glycan-containing sialoglycoprotein defining leukocyte differentiation and malignancy. 184 Feb 94

The oncoprotein 18 (Op18) gene encodes a proliferation-related cytosolic phosphoprotein, which is induced in normal lymphocytes following mitogenic stimulation. Studies of the Op18 gene are of particular interest because of the proposed role of Op18 protein in signal transduction and because of its occurrence in markedly increased amounts in acute leukemia cells. We have recently reported the cloning and sequencing of two cDNA clones for Op18 (1 and 1.5 kilobases). Both clones code for the same 149-amino acid polypeptide; however, they differ in their 3'-region as a result of alternative polyadenylation. We report here the sequencing of the Op18 gene and describe its expression in leukemia. The Op18 gene, which is 6.3 kilobases in length, is comprised of five exons and four introns and exhibits features that are common to other genes involved in cellular growth and proliferation. The increase in Op18 polypeptide in leukemia is associated with increased RNA transcription without gene amplification or rearrangement. Treatment of K562 leukemia cell line with hemin that induces terminal differentiation resulted in decreased expression of Op18. Our findings suggest that the high amount of Op18 protein in acute leukemia results from increased expression of a structurally unaltered gene.
...
PMID:Characterization of the gene for a proliferation-related phosphoprotein (oncoprotein 18) expressed in high amounts in acute leukemia. 191 19

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.
...
PMID:Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation. 193 60

The helix-loop-helix genes LYL, SCL and E2A are associated with chromosome translocations found in human lymphoid leukemias. To establish their hematopoietic expression patterns, we have isolated murine LYL and SCL cDNA clones and investigated the expression of all three genes by Northern blot analysis of 58 murine hemopoietic cell lines and tissues. The nucleotide sequences of LYL cDNA clones revealed alternative 5' untranslated sequences and differential splicing within the 5' portion of the coding region that may produce a LYL polypeptide lacking an N-terminal segment. The LYL gene was expressed in most myeloid, erythroid and B lymphocyte cell lines and displayed two alternative size classes of transcripts, the smaller size class (1.5-1.8 kb) being typical of the erythroid lineage and the larger class (2.0-2.3 kb) of the B cell lineage. These two size classes were found to differ in the 5' untranslated region. Thus, expression of the LYL gene appears to be differentially regulated in different hemopoietic cell types. In contrast, the E2A gene was expressed throughout the hemopoietic compartment as a single dominant transcript (3.5 kb). SCL expression was restricted to erythroid, mast and early myeloid cell lines, and the level of SCL transcripts (3.0 and 4.7 kb species) increased markedly during DMSO-induced differentiation of erythro-leukemia cells. Hence the SCL gene product may be an important regulatory factor for the erythroid lineage. The low or undetectable expression of both SCL and LYL in most T lymphoid cell sources is consistent with the view that the translocations of these genes in human T cell leukemias alter their normal regulation and may thereby contribute to neoplasia.
...
PMID:Differential expression of the LYL, SCL and E2A helix-loop-helix genes within the hemopoietic system. 200 Feb 19

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>