Gene/Protein Disease Symptom Drug Enzyme Compound
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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 generated and characterized three new monoclonal antibodies (mAbs), termed SN3, SN3a, and SN3b, which are directed to sialic acid of a glycoprotein(s) on human non-T leukemia cells. These mAbs were generated by immunizing mice with an antigen preparation isolated from cell-membrane glycoconjugates of NALM-1, a pre-B leukemia cell line. The initial characterization of the mAbs consisted of a sensitive cellular radioimmunoassay against various cultured human leukemia-lymphoma (HLL) and nonmalignant cell lines. They strongly reacted with all four (all three in the case of SN3a) non-T/non-B HLL cell lines tested and both pre-B HLL cell lines tested. However, they reacted with only one of three B HLL cell lines tested. In addition, these mAbs did not react with other cell lines, which include T- and myelomonocytic HLL cell lines and nonmalignant B-cell lines. Normal peripheral blood cells were also tested; the mAbs reacted with B cells and granulocytes but not with T cells, monocytes, erythrocytes, or platelets. In a test using SN3 and SN3b with uncultured cell specimens derived from various cancer patients, the mAbs primarily reacted with non-T/non-B and B HLL specimens, as well as with chronic myelocytic leukemia specimens. The biochemical nature of antigenic determinants defined by the three mAbs was studied by treating the non-T leukemia cells with sialidase and proteases. The results show that the antigenic determinants defined by these mAbs all contain a sialic acid residue(s) that is attached to the cells via a protein backbone(s). Competitive binding experiments show that binding of SN3 to the leukemia cells was blocked almost completely by SN3a and SN3b, as well as by BA-1. Both SN3 and SN3a are IgG1 antibodies, whereas SN3b is an IgM antibody; SN3b showed a strong complement-mediated cytotoxic activity against non-T leukemia cells.
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PMID:New monoclonal antibodies SN3, SN3a, and SN3b directed to sialic acid of glycoprotein on human non-T leukemia cells. 348 35

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

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

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

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