UMLS:C0023473 - FACTA Search

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Query: UMLS:C0023473 (chronic myeloid leukemia)
18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the biosynthesis of altered O-glycan structures on leukocytes from patients with chronic myelogenous leukemia and with acute myeloblastic leukemia (AML). It has been shown previously that the activity of CMP-NeuAc:Gal beta 1-3GalNAc alpha-R (sialic acid to galactose) alpha(2-3)-sialytransferase (EC 2.4.99.4) is increased in leukocytes from patients with chronic myelogenous leukemia (M. A. Baker, A. Kanani, I. Brockhausen, H. Schachter, A. Hindenburg, and R. N. Taub, Cancer Res., 47: 2763-2766, 1987) and with AML (A. Kanani, D. R. Sutherland, E. Fibach, K. L. Matta, A. Hindenburg, I. Brockhausen, W. Kuhns, R. N. Taub, D. van den Eijnden and M. A. Baker, Cancer Res., 50: 5003-5007, 1990). This increased activity may in part be responsible for the hypersialylation observed in leukemic leukocytes; however, hypersialylation may also be due to changes in underlying O-glycan structures. To test this hypothesis, we have assayed in normal human granulocytes and leukemic leukocytes several glycosyltransferases involved in the synthesis and elongation of the four common O-glycan cores. UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta(1-6)-GlcNAc transferase (EC 2.4.1.102), which synthesizes O-glycan core 2 (GlcNAc beta 1-6[Gal beta 1-3]GalNAc alpha), is significantly elevated in chronic myelogenous leukemia (4-fold) and AML (18-fold) leukocytes relative to normal human granulocytes. Neither normal nor leukemic cells show detectable activities of GlcNAc transferases which synthesize O-glycan core 3 (GlcNAc beta 1-3GalNAc-R) and core 4 (GlcNAc beta 1-6[GlcNAc beta 1-3] GalNAc-R) or the blood group I structure. The beta 3-GlcNAc transferase which elongates core 1 and core 2 was found at low levels in normal granulocytes but was not detectable in leukemic cells. The beta 3-GlcNAc transferase and beta 4-Gal transferase involved in poly-N-acetyllactosamine synthesis, as well as the beta 3-Gal transferase synthesizing core 1 (Gal beta 3 GalNAc), were present in all samples but were significantly increased in patients with AML. The observed changes are consistent with hypersialylation in leukemia.
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PMID:Biosynthesis of O-glycans in leukocytes from normal donors and from patients with leukemia: increase in O-glycan core 2 UDP-GlcNAc:Gal beta 3 GalNAc alpha-R (GlcNAc to GalNAc) beta(1-6)-N-acetylglucosaminyltransferase in leukemic cells. 199 66

We have examined granulocytes from patients with chronic myelogenous leukemia (CML) and from normal subjects to determine whether activity of a specific sialyltransferase might account for the aberrant sialylation of O-linked membrane oligosaccharides in CML cells. Total membrane preparations of morphologically mature CML and normal granulocytes were tested for sialyltransferase activity using the substrates galactosyl-beta 1-3-N-acetyl-D-galactosamine-alpha-O-nitrophenyl and N-acetyl-D-galactosamine-alpha-phenyl. N-Acetyl-D-galactosamine-alpha-phenyl was not an acceptor with either CML or normal cells. With galactosyl-beta 1-3-N-acetyl-D-galactosamine-alpha-O-nitrophenyl, sialyltransferase activity was 2.8 times higher in CML cells compared to normal cells. Product identification by high performance liquid chromatography showed that enzyme from both normal and CML granulocytes linked sialic acid to galactosyl-beta 1-3-N-acetyl-D-galactosamine-R by the alpha(2-3) and not the alpha(2-6) linkage. The enzyme CMP-N-acetylneuraminic acid: galactosyl-beta 1-3-N-acetyl-D-galactosamine-R alpha(2-3)-sialyltransferase has not previously been described in human granulocytes. The marked increase in activity of this enzyme in CML and the resulting increase in sialylation may contribute to the pathophysiological behavior of CML granulocytes.
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PMID:Presence of cytidine 5'-monophospho-N-acetylneuraminic acid:Gal beta 1-3GalNAc-R alpha(2-3)-sialyltransferase in normal human leukocytes and increased activity of this enzyme in granulocytes from chronic myelogenous leukemia patients. 347 17

Carbohydrate-specific surface labelling and 125I-labelled lectin binding techniques, in combination with one- or two-dimensional (non-reduced/reduced) SDS-polyacrylamide gel electrophoresis have been used with platelets from patients with myeloproliferation disorders and secondary thrombocytosis and from healthy donors. In essential thrombocythaemia platelet membrane glycoproteins were significantly less sialylated than in normals (particularly GP Ib and IIIa). Increased binding of 125I-labelled Lens culinaris lectin to thrombospondin and GP IIIa indicated a defect in the glucose/mannose glycosylation of the platelet glycoproteins in essential thrombocythaemia. In polycythaemia vera and in chronic myeloid leukaemia the terminal sialic acid of glycoprotein IIIb was labelled slightly more than normal. In chronic myeloid leukaemia there was increased labelling of the penultimate galactose/N-acetylgalactosamine residues of GP Ib, IIb, IIIa and IIIb. In comparison to myeloproliferative disorders, platelets from patients with secondary thrombocytosis showed no significant changes, except for platelets from two patients with idiopathic thrombocytopenic purpura which showed an increased sialylation of all surface glycoproteins.
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PMID:Platelet membrane glycoprotein abnormalities in patients with myeloproliferative disorders and secondary thrombocytosis. 400 82

The K562 cell line, which was established from a patient with chronic myeloid leukemia in blast crisis, was thought to be myeloid, but recent data indicate that it is an undifferentiated erythroid cell line. We have found that the glycosphingolipid content of these cells differs considerably from that of mature erythrocytes. Globotetraosylceramide, the most abundant glycolipid of mature red cells, was not detected in K562 cells, and neither was globotriaosylceramide. The predominant neutral glycolipids of K562 cells are monohexaosylceramides, which are a mixture of glucosyl- and galactosylceramides, and lactotriaosyl- and lactoneotetraosylceramides were also detected. Secondly, gangliosides which contain N-acetylgalactosamine were much more abundant than those containing N-acetylglucosamine in K562 cells, in contrast to erythrocytes. The most abundant ganglioside of K562 cells, GM2, is present in trace quantities in erythrocytes. A third major difference between these two cells lies in their relative proportions of neutral glycolipids and gangliosides. The molar ratio of neutral glycolipids/gangliosides is approximately 15:1 in erythrocytes and 1:1 in K562 cells. These striking differences between K562 cells and mature erythrocytes indicate that glycolipids may be useful cell surface markers of normal erythrocyte differentiation, and of erythroleukemias.
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PMID:Glycosphingolipids of K562 cells: a chemical and immunological analysis. 703 47

The neutral glycosphingolipids of hairy cells from a patient with hairy cell leukemia were chemically analyzed by thin-layer and gas-liquid chromatography, mass spectrometry, combined gas chromatography-mass spectrometry, and glycosidase treatment. These cells were found to have compounds containing one to four sugars with the following structures: Glc1 leads to 1Cer Gal beta 1 leads to 4Glc1 leads to 1Cer Gal alpha 1 leads to 4 Gal beta 1 leads to 4Glc1 leads to 1Cer GalNAc beta 1 leads to 3Gal alpha 1 leads to 4Gal beta 1 leads to 4Glc1 leads to 1Cer These compounds belong to the globo series of neutral glycosphingolipids and are similar to those found in human lymphocytes and chronic lymphocytic leukemia cells. They differ from the neutral glycosphingolipids found in human neutrophils and chronic myelogenous leukemia cells which are of the lactoneo and gala type. Neutral glycosphingolipids may be useful in classifying leukemias of uncertain origin.
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PMID:Neutral glycosphingolipids in hairy cell leukemia. 730 20

To elucidate control mechanisms of O-glycan biosynthesis in leukemia and to develop biosynthetic inhibitors we have characterized core 2 UDP-GlcNAc:Gal beta 1-3GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (EC 2.4.1.102; core 2 beta 6-GlcNAc-T) and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase (EC 2.4.99.4; alpha 3-SA-T), two enzymes that are significantly increased in patients with chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML). We observed distinct tissue-specific kinetic differences for the core 2 beta 6-GlcNAc-T activity; core 2 beta 6-GlcNAc-T from mucin secreting tissue (named core 2 beta 6-GlcNAc-T M) is accompanied by activities that synthesize core 4 [GlcNAc beta 1-6(GlcNAc beta 1-3)GalNAc-R] and blood group I [GlcNAc beta 1-6(GlcNAc beta 1-3)Gal beta-R] branches; core 2 beta 6-GlcNAc-T in leukemic cells (named core 2 beta-GlcNAc-T L) is not accompanied by these two activities and has a more restricted specificity. Core 2 beta 6-GlcNAc-T M and L both have an absolute requirement for the 4- and 6-hydroxyls of N-acetylgalactosamine and the 6-hydroxyl of galactose of the Gal beta 1-3GalNAc alpha-benzyl substrate but the recognition of other substituents of the sugar rings varies, depending on the tissue. alpha 3-sialyltransferase from human placenta and from AML cells also showed distinct specificity differences, although the enzymes from both tissues have an absolute requirement for the 3-hydroxyl of the galactose residue of Gal beta 1-3GalNAc alpha-Bn. Gal beta 1-3(6-deoxy)GalNAc alpha-Bn and 3-deoxy-Gal beta 1-3GalNAc alpha-Bn competitively inhibited core 2 beta 6-GlcNAc-T and alpha 3-sialyltransferase activities, respectively.
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PMID:Processing O-glycan core 1, Gal beta 1-3GalNAc alpha-R. Specificities of core 2, UDP-GlcNAc: Gal beta 1-3 GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase. 829 5

A lectin, Crenomytilus grayanus (CGL), was purified from sea mussel C. grayanus by affinity chromatography on acid-treated Sepharose 6B and following gel filtration on Sephacryl S-200. Molecular weight of the lectin obtained was determined by SDS-PAGE to be 18,000, independent of the presence or absence of beta-mercaptoethanol. CGL was found to agglutinate all types of the human erythrocytes together with mouse and rabbit. In hemagglutination inhibition assays, N-acetyl-D-galactosamine, D-galactose, and D-talose were the most potent inhibitors among the monosaccharides tested. Out of the oligosaccharides containing nonreducing terminal D-galactose, melibiose, and raffinose were found to be strong inhibitors. On the other hand, among the glycoproteins, asialo-BSM was the best inhibitor. The hemagglutinating activity of CGL was independent of the divalent cations Ca2+ and Mg2+. Significant CGL activity was observed between pH 8-10.
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PMID:Isolation and characterization of new GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus. 956 72

The author engaged himself in the studies of ABO blood group system for the last three decades, and reviewed the progresses in this period, which were classified into following 5 items. 1. H-, A- and B-active oligosaccharides were isolated from the globoside fractions from human erythrocytes by ozonolysis. One of the H-active oligosaccharide with short carbohydrate chain is a pentasaccharide: Fuc(alpha 1-->2)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc, and the other with long carbohydrate chain is a heptasaccharide: Fuc(alpha 1-->2)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc. Hexa- or octasaccharides with blood group A- or B-activity have an additional alpha-N-acetylgalactosaminyl residue or alpha-galactosyl residue, which joints with alpha 1-->3 linkage to subterminal beta-galactose of the both of H-active oligosaccharides, respectively. 2. A blood group A-gene specified alpha-N-acetyl-galactosaminyltransferase (A-enzyme) catalyzes the transfer of N-acetylgalactosamine from the UDP-sugar to the subterminal beta-galactosyl residue of blood group H-active carbohydrate chain, and a blood group B-gene specified alpha-galactosyltransferase (B-enzyme) catalyzes the transfer of galactose from the UDP-sugar to the subterminal beta-galactosyl residue of blood group H-active carbohydrate chain, respectively. Either the A- or B-enzyme can not transfer the substrate sugar to the carbohydrate chain lacking alpha-fucosyl residue of H-determinant, and it is the reason why the synthesis of blood group A- or B-antigenic structure in inhibited in the tissues of Bombay phenotype and in the secretory glands of the nonsecretor. 3. Specific antibody either to the A- or B-enzyme can be introduced in the serum of the rabbit which was immunized with the A- or B-enzyme preparation, respectively. And immunological cross reaction is also present between the A- and B-enzyme, but the immunologically cross reactive material can not be found in the blood group O individual. The absence of immunologically cross reactive material in the blood group O individual is supported by a fact that the cross reactive antibody similar to the antibody in rabbit serum was present in the serum of the chronic myeloid leukemia patient, who was belonged to blood group B and treated with blood group incompatible bone marrow transplantation from blood group O donor, because it is acceptable to speculate that the grafted lymphocytes react to the B-enzyme in the recipient and produce the anti-enzyme antibody. 4. The immunological profiles described above are compatible with the cDNA structures of human blood group ABO alleles presented by Yamamoto F. et al. Their gene model is that the cDNAs of blood group ABO alleles are highly homologous, but the cDNA of common O allele is non-functional due to a single nucleotide deletion close to the 5'end of the coding sequence, which causes a frame shift of the codon, and results in truncated peptide. 5. Transcription of the human blood group ABO gene can be enhanced by a CBF/NF-Y which binds the minisatellite on the 5'-upstream sequence of the gene.
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PMID:[Past and present studies on ABO blood group system]. 1007 71

Sialic acids as terminal residues of oligosaccharide chains play crucial roles in several cellular recognition events. Exploiting the selective affinity of Achatinin-H toward N-acetyl-9-O-acetylneuraminic acid-alpha2-6-GalNAc, we have demonstrated the presence of 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)-GPs) on lymphoblasts of 70 children with acute lymphoblastic leukemia (ALL) and on leukemic cell lines by fluorimetric HPLC and flow cytometric analysis. This study aims to assess the structural aspect of the glycotope of Neu5,9Ac(2)-GPs(ALL) and to evaluate whether these disease-specific molecules can be used to monitor the clinical outcome of ALL. The Neu5,9Ac(2)-GPs(ALL) were affinity-purified, and three distinct leukemia-specific molecular determinants (135, 120, and 90 kDa) were demonstrated by SDS-PAGE, western blotting, and isoelectric focusing. The carbohydrate epitope of Neu5,9Ac(2)-GPs(ALL) was confirmed by using synthetic sialic acid analogs. The enhanced presence of anti-Neu5,9Ac(2)-GP(ALL) antibody in ALL patients prompted us to develop an antigen-ELISA using purified Neu5,9Ac(2)-GPs(ALL) as coating antigens. Purified antigen was able to detect leukemia-specific antibodies at presentation of disease, which gradually decreased with treatment. Longitudinal monitoring of 18 patients revealed that in the early phase of the treatment patients with lower anti-Neu5,9Ac(2)-GPs showed a better prognosis. Minimal cross-reactivity was observed in other hematological disorders (n = 50) like chronic myeloid leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma as well as normal healthy individuals (n = 21). This study demonstrated the potential of purified Neu5,9Ac(2)-GPs(ALL) as an alternate tool for detection of anti-Neu5,9Ac(2)-GP antibodies to be helpful for diagnosis and monitoring of childhood ALL patients.
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PMID:Purification and characterization of 9-O-acetylated sialoglycoproteins from leukemic cells and their potential as immunological tool for monitoring childhood acute lymphoblastic leukemia. 1519 7

Carbohydrate N-acetylgalactosamine 4-0 sulfotransferase 9 (CHST9) belongs to the N-acetylgalactosamine 4-sulfotransferase (GalNAc4ST) family. A recent array-based study implicated the presence of copy-number variations (CNV) of the region encompassing CHST9 in the genomes of acute myelogenous leukemia. Most of the current studies, however, focused on the genome-wide screening of CNV, and the functional impact of such regions needs to be extensively investigated in large amounts of clinical samples. In our study, we collected 617 bone marrow samples from multi-types of hematologic malignancies, as well as healthy controls, and detected the CNV of CHST9 by real-time polymerase chain reaction (PCR). We found significant association between the CNV of CHST9 and these hematologic malignancies including acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, multiple myeloma, and myelodysplastic syndrome. We also examined CHST9 mRNA expression in the samples with one or two copies of DNA, and observed a weak yet positive correlation between the relative expression level and gene dosage. In general, the CNV of CHST9 have been shown to associate with hematologic malignancies. The functional consequences of CNV, however, need to be investigated extensively in the future.
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PMID:Examination of copy number variations of CHST9 in multiple types of hematologic malignancies. 2115 30

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