Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polylactosaminoglycans were isolated from human chronic myelogenous leukemia cells and their structures were elucidated. The lactosaminoglycan saccharides were isolated by hydrazinolysis and fractionated by QAE-Sephadex. The structures of fractionated oligosaccharides were analyzed by fast atom bombardment-mass spectrometry and methylation before and after treatment with specific exoglycosidases, such as alpha 2----3 specific neuraminidase. Based on these experiments, the structures of sialyl polylactosaminoglycans of chronic myelogenous leukemia cells were found to contain the following unique structure which is absent in normal mature granulocytes: (formula; see text) In addition to this, chronic myelogenous leukemia polylactosaminoglycans can be distinguished from normal granulocyte polylactosaminoglycans by the following characteristics. Leukemic polylactosaminoglycans are (a) shorter, (b) more highly sialylated and contain fully sialylated, tetrasialosyl polylactosaminoglycans, (c) are less fucosylated at C-3 of N-acetylglucosamine of polylactosaminyl side chains, and (d) contain a significant amount of sialyl Lex, NeuNAc alpha 2----3Gal beta 1----4(Fuc alpha 1----3)GlcNAc beta 1----3, structure. These results indicate that chronic myelogenous leukemia cells express unique polylactosaminoglycan structures which are distinct from normal mature granulocytes.
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PMID:Structures of sialylated fucosyl polylactosaminoglycans isolated from chronic myelogenous leukemia cells. 386 14

Lysosomal arylsulfatases A and B of peripheral leukocytes from patients with chronic myelogenous leukemia and from healthy subjects were studied. Two enzyme activities of leukemia cells were significantly higher than those of cells from healthy subjects, irrespective of total and differential counts of leukemic cells. Upon anion-exchange chromatography, the arylsulfatases of chronic myelogenous leukemia cells and normal leukocytes were separated into the basic B enzyme and its anionic variant (B1) and A enzyme. However, the amount of B1 enzyme relative to B enzyme or the activity ratio of B1 enzyme to total arylsulfatase B (B + B1) was higher in chronic myelogenous leukemia cells than in normal cells. The anionic property of the enzyme was found to be due to phosphate groups bound to the carbohydrate moiety of the arylsulfatase, based on the following results. When B1 enzyme was treated with alkaline phosphatase followed by isoelectric focusing, it was changed to a less anionic enzyme with heterogeneous components which are ascribed to phosphodiester groups linked to the heterogeneous carbohydrate moiety of the enzyme; no effect was observed by sialidase treatment. Upon treatment of B1 enzyme with endo-beta-N-acetylglucosaminidase H, which cleaves sugar chains of a high mannose type in glycoproteins, the anionic heterogeneous components were converted to the basic component similar to B enzyme. From our present and previous observations, it can be concluded that the increase of phosphorylated forms of the lysosomal hydrolase represents one characteristic of rapidly proliferating neoplastic cells.
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PMID:Lysosomal arylsulfatases of human leukocytes: increment of phosphorylated B variants in chronic myelogenous leukemia. 613 78

We report a case of chronic myelogenous leukemia (CML) associated with pronounced peripheral lymphadenopathy, with the cells having the philadelphia (Phl) chromosome and T-cell features. A 23-year-old man who was diagnosed as having CML and treated with busulfan was admitted to our hospital because of increasing hepatosplenomegaly and pronounced lymphadenopathy. An axillary lymph node biopsy disclosed that the malignant cells formed rosettes with neuraminidase-treated sheep red blood cells (En) (95.0%) and were positive for Leu 1 (91.8%). Of the cytochemical reactions, peroxidase was negative and periodic acid-Shiff, acid alpha-naphthyl acetate esterase and beta-glucuronidase were all positive. The karyotype of the bone marrow cells was 46 XY Phl positive (22q-), and that of the lymph node cells was 51 XY Phl positive +8, +9, +18, +19, +21, 22q-. He was treated with various anti-leukemic agents and irradiation. Despite such treatments, he died of pneumonia. This is a report of a CML patients with blast crisis and tumor formation characterized by T-cell features.
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PMID:Blast crisis of chronic myelogenous leukemia with tumor formation characterized by T-cell features--a case report. 660 8

R-type vitamin B12 binding proteins (R proteins) from human granulocytes, erythrocytes, plasma, and other body fluids were characterized by isoprotein banding patterns on autoradiograms after resolution via thin-layer polyacrylamide isoelectric focusing (IEF) gel electrophoresis. R proteins obtained from various tissue sources in a given individual show tissue-specific electrophoretic patterns. The desialated R proteins obtained following in vitro treatment with neuraminidase are, however, the same for any given individual and do not show tissue specificity. The differences seen in native R proteins (i.e., transcobalamin I, III, and others) obtained from different tissues are due to variations only in the sialic acid content. Granulocytes from patients with chronic myelogenous leukemia (CML) contain both TC I and TC III, and these R proteins can be released in vitro by lithium stimulation. Normal granulocytes contain only TC III. Differences in desialated R proteins from individual to individual are due to a genetic polymorphism controlled by a single genetic locus (designated TCR) with two alleles, 1 and 2, which are found to be codominantly expressed in heterozygous individuals. The allelic variants of the desialated R proteins found in different blood cells and body fluids are controlled by only one genetic locus.
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PMID:The biochemical and genetic basis for the microheterogeneity of human R-type vitamin B12 binding proteins. 694 16

The sialic acid content of erythrocytes from healthy individuals of different blood types and of patients with known hematological disorders has been determined. The sialic acid was completely released enzymatically with sialidase and quantitated by the thiobarbituric acid method. The sialic acid content of erythrocytes was constant irrespective of ABO blood type, or anticoagulant used; viz, 0.85-0.92 mumoles/ml of packed erythrocytes or 46-53 X 10(6) sialyl residues per cell. Deviations from these normal values were obtained with erythrocytes from patients with a variety of hematological disorders. Patients with the following disorders have significantly (P less than 0.01) lower sialic acid values compared to erythrocytes from healthy individuals (given in the order of decreasing sialic acid content): sickle cell anemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelomonocytic leukemia, non-Hodgkin lymphocytic lymphoma, chronic granulocytic leukemia, acute myelocytic leukemia, leukemia, and Hodgkin disease.
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PMID:Sialic acid content of erythrocytes in normal individuals and patients with certain hematologic disorders. 721 33

The mAb A6 was produced by immunization of mice with human PHA-stimulated PBMC. Immunoprecipitation studies and staining of cell lines transfected with individual leukocyte common antigen (LCA) isoforms showed that A6 recognizes a unique epitope strongly expressed on the lower MW isoform (p180) of LCA, but also weakly expressed on the p190 isoform coded by exon B and the p205 coded by exons A and B. The epitope recognized by A6 was carbohydrate-dependent in that it was neuraminidase-sensitive, but trypsin-resistant. A6 strained most TCR-alpha beta+ cells with differential intensities, subdividing them into a bright and dim population, and strongly stained all TCR-gamma delta+ cells. A6 did not stain CD19+ B cells nor CD56+ NK cells. Anti-CD45 mAb such as UCHL1 recognizing CD45RO have been used to define memory T cells. Depletion of PBMC subsets with A6 or UCHL1 mAb dramatically decreased proliferative responses to the recall antigens anti-CD3 mAb and alloantigen and enhanced their responses to PHA. A6, unlike UCHL1, also depleted alloreactive T cells that affect primary and secondary MLC and CML. Thus, A6 was shown to recognize the lower MW isoforms of LCA which are expressed on functional T cell subsets including memory, activated, and alloreactive T cells.
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PMID:A monoclonal antibody (A6) recognizing a unique epitope restricted to CD45RO and RB isoforms of the leukocyte common antigen family identifies functional T cell subsets. 752 74

Chronic myelogenous leukemia (CML) granulocytes exhibit a number of characteristics attributable to immature granulocytes, including marked increases in cell surface sialylation of glycoproteins which may be due, at least in part, to an increased activity of cytidine 5'-monophosphate-N-acetylneuraminic acid:Ga1 beta 1-3Ga1NAc alpha(2-3)-sialyltransferase (EC 2.4.99.4), and perhaps to altered activity of other glycosyltransferases and sialidases. This aberrant sialylation of CML granulocytes contributes to the decreased binding of the synthetic chemotactic peptide, formyl Met Leu Phe (fMLP), to the surface of CML granulocytes which leads to a rapid, transient increase in cytosolic free calcium ([Ca2+]i), an integral step in the biochemical cascade leading to cell activation. To determine if the decrease in binding of fMLP to CML granulocytes translates into a functional deficit, we measured fMLP-induced increases in [Ca2+]i. Compared to normal granulocytes, fMLP-induced increases in [Ca2+]i were markedly decreased in CML granulocytes. After sialidase treatment, a significant augmentation in fMLP-induced increases in [Ca2+]i was noted in CML granulocytes, indicating that the decreased signalling may be a consequence of aberrant sialylation. To determine if the effects of aberrant sialylation also alters the binding of endogenous polypeptide mediators, we determined the effect of desialylation of CML and normal granulocytes on binding of the colony stimulating factor for granulocytes and monocytes (GM-CSF), which plays a role in differentiation and proliferation of myeloid-lineage cells. As with fMLP binding, we also showed that the binding of GM-CSF to CML granulocytes, but not normal granulocytes, was markedly increased after sialidase treatment. Similarly, binding of GM-CSF to undifferentiated HL-60 cells was markedly increased after sialidase treatment. Therefore, we have demonstrated that aberrant sialylation of CML granulocytes not only alters the binding of fMLP and GM-CSF to their receptor(s), but may also alter signal transduction. Thus, aberrant glycosylation of CML granulocytes may reduce the binding of hematopoietic growth factors, which in turn may be responsible for the immature phenotype of CML granulocytes.
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PMID:Role of aberrant sialylation of chronic myeloid leukemia granulocytes on binding and signal transduction by chemotactic peptides and colony stimulating factors. 822 Jan 57

Estimation of CD34 expression is widely used to detect and quantify progenitor cells in haemopoietic tissues used as stem cell sources for transplantation. Mouse monoclonal antibodies to CD34 recognise different epitopes of the mucin-like sialoglycoprotein. These epitopes can be grouped into three classes by their differing sensitivities to the enzymes: neuraminidase, chymopapain and glycoprotease. We have compared the expression, by flow cytometry, of the three CD34 epitopes on normal adult and fetal haemopoietic tissue and in chronic myeloid leukaemia, and have used four antibodies from each class to assess variability of staining within and between epitope classes. The results reveal variable expression of CD34 both within and between tissue types and antibody classes. As a result of the different levels of detection by different antibodies, the apparent number of CD34-positive cells vary by approximately 6-fold. Enrichment for CD34 cells using magnetic bead technology shows a significant difference in the percentage of CD34 cells detected for two of the epitope types.
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PMID:Extent of variability inherent in measurements of CD34-positive cells in different human haemopoietic tissues. 852 80

Granulocytes from patients with chronic myeloid leukemia (CML) egress from the bone marrow before they are functionally mature and exhibit delayed emigration to sites of infection. To understand these defects, we have compared the binding of normal and CML granulocytes to the 293 cell line transfected with cDNA for P-selectin. The CML granulocytes show significantly reduced binding to P-selectin relative to normal cells. The binding of normal granulocytes to P-selectin was significantly reduced when the cells were treated with anti CD15, polyclonal anti-P-selectin, monoclonal anti-P-selectin (G1) antibodies or neuraminidase. On average, only 8% of the CML granulocyte population bound to P-selectin. The antibodies and neuraminidase were ineffective in inhibiting the binding of this population of leukemic cells. These data show that the morphologically mature CML granulocytes consist of a heterogeneous population of cells, some of which do not bind to P-selectin and others which adhere to the molecule via modified sugars.
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PMID:Chronic myeloid leukemic granulocytes exhibit reduced and altered binding to P-selectin: modification in the CD15 antigens and sialylation. 902 87

In chronic myeloid leukemia K562 cells, differentiation is also blocked because of low levels of ganglioside GM3, derived by the high expression of sialidase Neu3 active on GM3. In this article, we studied the effects of Neu3 silencing (40-70% and 63-93% decrease in protein content and activity, respectively) in these cells. The effects were as follows: (a) gangliosides GM3, GM1, and sialosylnorhexaosylceramide increased markedly; (b) cell growth and [(3)H]thymidine incorporation diminished relevantly; (c) as mRNA, cyclin D2, and Myc were much less expressed, whereas cyclin D1 was expressed more like its inhibitor p21; (d) as mRNA, pro-apoptotic proteins Bax and Bad increased with concurrent decrease and increase in the anti-apoptotic proteins Bcl-2 and Bcl-XL, respectively; (e) the apoptosis inducers etoposide and staurosporine were active on Neu3 silencing cells but not on mock cells; (f) as mRNA, the megakaryocytic markers CD10, CD44, CD41, and CD61 increased similar to the case of mock cells stimulated with PMA; (g) the signaling cascades mediated by PLC-beta2, PKC, RAF, ERK1/2, RSK90, and JNK were largely activated. The induction of a GM3-rich ganglioside pattern in K562 cells by treatment with brefeldin A elicited a phenotype similar to that of Neu3 silencing cells. In conclusion, upon Neu3 silencing, K562 cells show a decrease in proliferation, propensity to undergo apoptosis, and megakaryocytic differentiation.
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PMID:Silencing of membrane-associated sialidase Neu3 diminishes apoptosis resistance and triggers megakaryocytic differentiation of chronic myeloid leukemic cells K562 through the increase of ganglioside GM3. 1882 Jun 43


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