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 glycosylation of beta-hexosaminidase was investigated in the transformed cell-line, CCRF/CEM, derived from a human acute lymphoblastic leukaemia, and comparisons were made with enzyme from normal human skin fibroblasts. A series of studies including neuraminidase sensitivity, lectin chromatography, Biogel P4 chromatography of [3H]-mannose-labelled glycopeptides and endoglycosidase susceptibility, provided clear evidence that in CCRF/CEM cells, beta-hexosaminidase was abnormally glycosylated. The results indicate that leukemia-associated changes in beta-hexosaminidase expression are probably due to increased sialylation of highly-branched complex oligosaccharides.
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PMID:The nature of lysosomal enzyme glycosylation in ALL: relevance to abnormal beta-hexosaminidase expression. 296 80

Fv-4r is a dominant resistance gene which controls resistance of mice to exogenous infection with ecotropic murine leukemia viruses. Cell lines with various degrees of resistance to ecotropic Friend murine leukemia virus infection were established from BALB/c-Fv-4wr mice which are partially congenic with BALB/c. The degree of resistance of these cell lines correlated well to the amount of glycoprotein with mol wt 80 K on cell surface. The resistance of cells was reduced by the treatment of glycosylation inhibitors, tunicamycin and 2-deoxy-D-glucose. The results indicate that the Fv-4 resistance is ascribed to the unique glycoprotein on cell surface.
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PMID:Relationship between the cellular resistance to Friend murine leukemia virus infection and the expression of murine leukemia virus-gp70-related glycoprotein on cell surface of BALB/c-Fv-4wr mice. 300 21

The understanding of the differentiation process of lymphocytes in the embryonic thymus has been based on extrapolation from adult thymic lymphocytes. The study presented here was mainly concerned with the new cell surface antigens designated FT (FT-1, FT-2), which are expressed on fetal thymocytes of all mouse strains examined, but not on thymocytes or any other lymphoid cells of adult mice. One of the interesting features of FT antigens is the timing of their expression in connection with the ontogeny of thymic lymphocytes. A majority of fetal thymocytes at the 13th day of gestation express FT antigens, whereas no positive cells are found in fetal liver. Therefore, FT antigens seem to appear as soon as the stem cells have reached the thymus. The proportion of FT+ cells then declines sharply with increase in the time of gestation, while Thy-1+ cells increase in inverse proportion. All of these results seem to support the idea that the thymocytes expressing FT antigens are replaced with Thy-1+ thymocytes, although the possibility of the transition from FT+ to Thy-1+ cells cannot be excluded. It was also demonstrated that fetal thymocytes are heterogeneous with respect to the expression of FT-1 and FT-2 antigens. Especially, thymic lymphocytes at the earlier stages of ontogeny can be divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-. With the emergence of Lyt antigens, these subpopulations seem to differentiate and acquire far more complicated features. Such cellular heterogeneity probably reflects the complexed events like selection, deletion or amplification occurring in the embryonic thymus. Another interesting aspect of FT antigens is their reappearance on the surface of thymic leukemia cells. Biochemical studies have indicated that the molecular weight of FT-1 antigen on leukemia cells is about 100,000 by means of biosynthetic labeling with either [3H]-galactose or [35S]-methionine. FT-1 antigen on fetal thymocytes also appeared as a major band with m.w. 100,000. Two-dimensional gel electrophoresis revealed that FT-1 antigenic determinants appear to reside on a family of glycoproteins with extensive charge heterogeneity. All of these results suggest that FT antigens, especially FT-1 antigen, will be useful markers for understanding the mechanism underlying the activation of normally silent genetic information in leukemia cells. In summary, further biochemical and genetic analysis of FT antigens will contribute to an understanding of the ontogenic development of T cells as well as the leukemogenesis of T cell leukemias.
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PMID:[T cell leukemia antigens, FT-1 and FT-2]. 308 84

A human homologue of the recently cloned murine leukemia-inhibitory factor (LIF) gene was isolated from a genomic library by using the murine cDNA as a hybridization probe. The nucleotide sequence of the human gene indicated that human LIF has 78% amino acid sequence identity with murine LIF, with no insertions or deletions, and that the region of the human gene encoding the mature protein has one intervening sequence. After oligonucleotide-mediated mutagenesis, the mature protein-coding region of the LIF gene was introduced into the yeast expression vector YEpsec1. Yeast cells transformed with the resulting recombinant could be induced with galactose to produce high levels of a factor that induced the differentiation of murine M1 leukemic cells in a manner analogous to murine LIF. This factor competed with 125I-labeled native murine LIF for binding to specific cellular receptors on murine cells, compatible with a high degree of structural similarity between the murine and human factors.
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PMID:Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor. 312 91

Mannose in animal cells is phosphorylated by hexokinase (HK) and later isomerised by mannose phosphate isomerase (MPI) to fructose-6-P, which is incorporated in the glycolysis pathway. In this paper we report a significant decrease of MPI activity in splenic lymphoid cells from AKR/J old mice with lymphocytic leukaemia in comparison to that found in splenic lymphocytes from AKR/J non-leukaemic young mice and BALB/c young and old control mice. However, HK with mannose as substrate presents a normal activity in AKR/J leukaemic mice. This marked shortage of MPI explains the in vitro mannose toxicity found by us here in splenic lymphoid cells from AKR/J leukaemic mice. MPI activity was also decreased in peripheral blood lymphocytes from 4 out of the 6 patients studied with chronic lymphocytic leukaemia in relation to the activity found in the lymphocytes from healthy donors. The utility of analysing MPI activity in leukaemia patients and the use of mannose as an innocuous chemotherapic supporting agent in patients with decreased MPI activity is proposed.
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PMID:Enzymes of mannose metabolism in murine and human lymphocytic leukaemia. 321 65

Because of carbohydrate alterations in malignant cells, serum glycoproteins have drawn considerable attention. In the current investigation we determined total sialic acid (TSA), lipid bound sialic acid (LSA), protein bound hexoses (galactose + mannose), fucose, hexosamines (galactosamine + glucosamine) and mucoid protein concentrations in the serum of patients with anemia and myeloid leukemia. The results were compared with those obtained in healthy individuals. In the leukemia patients we observed significant increases in glycoconjugates compared with the controls (P less than 0.001), and in TSA and fucose levels compared with the anemia patients (P less than 0.001). LSA and hexosamine levels were significantly lower in anemia patients with respect to the leukemia patients (P less than 0.01 and P less than 0.05 respectively), whereas levels of mucoid proteins and hexoses did not show significant differences. Except for hexosamines, all the markers tested were significantly elevated in the anemia patients compared with the controls. The present study suggests that the glycoconjugates investigated might be useful biochemical markers for differentiating anemic from leukemic conditions.
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PMID:Serum glycoconjugates in patients with anemia and myeloid leukemia. 323 7

Interleukin 3 (IL-3) derived from mouse T cells was biosynthetically labeled with either [35S]methionine or [3H]mannose, affinity-purified using various anti-IL-3 antibodies, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography revealed the same three major bands with Mr values of 21,500-22,500, 27,000-31,000, and 32,000-36,000, irrespective of whether the anti-IL-3 antibody had been directed to the N or C termini of the IL-3 polypeptide. Bioassay of eluates from the gels confirmed that all three bands exhibited IL-3 bioactivity. IL-3 produced from two nonphysiological sources, the myelomonocytic leukemia WEHI-3B or Cos 7 cells that had been transfected with an IL-3 cDNA clone, had in each case a different pattern of microheterogeneity. Treatment with either tunicamycin or N-glycanase resulted in IL-3 running as one band with Mr 16,000, corresponding to its 140-amino acid polypeptide chain. No evidence for proteolytic processing was detected. These results show that the Mr heterogeneity of IL-3 was highly dependent on the cellular source and is due to N-linked glycosylation.
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PMID:Multiple glycosylated forms of T cell-derived interleukin 3 (IL-3). Heterogeneity of IL-3 from physiological and nonphysiological sources. 326 13

Nonphosphorylative transglycosylation was determined both against p-nitrophenyl-N-maltoside and maltose with p-nitrophenyl-N-glucoside in serum and liver of mice with transplantable leukemia P 388 and L 1210. Histopathological verification of lymph nodes, spleen and liver of all used mice was carried out. Significant increase of transglycosylating activity in serum of P 388 mice and simultaneously decrease enzymatic activity in liver was observed. Moreover decrease of examined activity in serum and liver of L 1210 mice was demonstrated. The donor properties of some sugar in transglycosylation reaction was investigated.
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PMID:[Non-phosphorylative transglycosylation in the serum and liver of mice with transplantable leukemia P388 and L1210]. 343 86

HL-60 promyelocytic leukemia cells were induced to differentiate along the granulocytic pathway by exposure to 6-methylmercaptopurine ribonucleoside (6-MMPR). The interference with cellular replication and the induction of terminal maturation by 6-MMPR appeared to be a consequence of the inhibition of purine nucleotide biosynthesis de novo, since the simultaneous exposure of HL-60 cells to 6-MMPR and adenine completely prevented cellular differentiation, as measured by both nitro-blue tetrazolium reduction and the phagocytosis of latex beads, and partially prevented growth inhibition. The induction of HL-60 leukemia cell maturation by 6-MMPR was preceded by a marked reduction in the incorporation of [3H]mannose into glycoproteins and into the dolichol-oligosaccharide precursors of N-linked glycoprotein biosynthesis. Simultaneous exposure of HL-60 cells to 6-MMPR and adenine completely prevented the reduction in [3H]mannose incorporation into glycoproteins produced by the purine nucleoside antimetabolite. These findings suggest that the utilization of mannose for glycoprotein biosynthesis may be a component of the mechanism by which 6-MMPR causes the induction of the terminal differentiation of HL-60 leukemia cells.
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PMID:Inhibition of the synthesis of glycoproteins and induction of the differentiation of HL-60 promyelocytic leukemia cells by 6-methylmercaptopurine ribonucleoside. 347 42

We analyzed the patterns of glycosphingolipids (GSLs) from a line of cells derived from a clone of the human T-cell leukemia cells (CEM) that had been induced to differentiate by phorbol-12-myristate-13-acetate (PMA) into cells with a suppressor-like phenotype. We characterized the differentiation state of the cells by immunofluorescence by using anti-cell surface differentiation-specific monoclonal antibodies (OKT3, OKT4, OKT6, and OKT8). The GSLs were extracted and separated by thin-layer chromatography and the individual bands were quantitated by a dual-wavelength densitometer or by autoradiography of GSLs labeled with [14C]glucosamine and [14C]galactose. Treatment of the CEM cells with 0.16-16 nM PMA for 6 h to 6 days resulted in a dose- and time-dependent increase in the amount of two neutral GSLs [ceramide monohexoside and ceramide dihexoside] and three gangliosides [monosialoganglioside (GM3), sialosylparagloboside, and disialoganglioside (GD3)]. The increase in the neutral GSLs after PMA treatment reached its maximum at 30 h while GM3 peaked at 96 h. The increases in GM3 and sialosylparagloboside are presumably due to an increase in their synthesis levels because PMA promoted an elevated incorporation of glucosamine and galactose into these GSLs. The increase in the amount of GD3, on the other hand, is due to either a decrease in its degradation or use in other metabolic pathways because no detectable increase in glucosamine and galactose incorporation into this ganglioside could be found. Incubation of control or PMA-induced CEM cells with GM3 fractions purified from either CEM cells, human brain, or dog erythrocytes caused a reduction in cell growth and prevented the increase in reactivity of the induced cells with the OKT3 antibody. Incubation with semisynthetic ceramide dihexoside, however, prevented the decrease in reactivity with the OKT4 antibody. The observed changes in GSL patterns during PMA-induced differentiation of the CEM cells into suppressor-like cells and the inhibition of CEM cell growth by GM3 fractions suggest that the GSLs play a role in the control of cell growth and differentiation in the PMA-treated CEM cells.
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PMID:Alteration in glycosphingolipid pattern during phorbol-12-myristate-13-acetate-induced cell differentiation in human T-lymphoid leukemia cells. 348 42


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