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)

Forty patients with different varieties of leukaemia and lymphoma were studied before and after therapy. Red cells and lymphocytes from each patient were tested for foetal antigen by lectin-agglutination test. The antigen was detectable on red cells in all untreated cases, the highest titre being found in chronic myeloid leukaemia. The titre showed significant reduction after treatment in all cases. We conclude that foetal antigen on red cells is a useful diagnostic aid in haematological malignancy and is a good indicator of the outcome of therapy.
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PMID:Study of foetal antigen in haematological malignancy. 145 63

In a search for mechanisms of potential graft-versus-leukaemia (GVL) activity after allogeneic bone marrow transplantation (BMT), peripheral lymphocytes from five patients (four chronic myeloid leukaemia, one acute lymphoblastic leukaemia) 24-39 days post-transplant were precultured with pretransplant host leukaemia cells and then cloned by limiting dilution with interleukin-2 (IL-2). Clones obtained were exclusively CD3+ CD56-, carried the alpha/beta form of the T cell receptor for antigen, and were mostly (88% of 138) CD4+. None of 143 clones, including CD8+ clones, convincingly lysed host pretransplant cells, although 35 (24.5%) manifested lytic potential in lectin-mediated cytotoxicity assays. Measuring the proliferative responses of 118 of these clones in the presence of exogenous IL-2 revealed that a small number of clones reacted more strongly to host leukaemia than to unrelated leukaemias or B lymphoblastoid cell lines. In the two cases tested, the donor's untransplanted lymphocytes cloned under the same conditions as post-transplant cells did not generate any clones reacting preferentially with host leukaemia cells. These results may suggest that some T cells appearing shortly after allogeneic BMT could potentially mediate anti-leukaemia activity not associated with cytolysis of target cells.
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PMID:Cytotoxic and proliferative functions of T lymphocyte clones derived very shortly after allogeneic bone marrow transplantation. 193 51

Granulocytes from patients with chronic myelogenous leukemia (CML) are morphologically identical to their normal counterparts but show marked differences in circulation patterns and in some membrane properties. We have previously shown that there is abnormal lectin binding to CML granulocytes, and aberrant sialylation of membrane glycoproteins. To examine the changes in sialylation of CML granulocytes further, we have studied membrane preparations from CML and normal granulocytes for specific sialyltransferase activity. Because sialyltransferase enzymes are specific for the configuration of the acceptor group, enzyme activity was assayed by measuring transfer of sialic acid from CMP-14C-sialic acid to substrates of defined structure. As compared with those of normal counterparts, CML extracts catalyzed a 50% higher overall rate of sialylation of asialofetuin, a substrate possessing both N- and O-linked acceptors. Studies of enzyme specificity utilizing porcine and ovine submaxillary mucins, antifreeze glycoprotein and alpha-1 acid glycoprotein as acceptors showed that the increased sialylation by CML extracts was due primarily to substrates with the O-linked Gal beta 1----3GaINAc acceptor group. These data suggest that sialyltransferase activity is increased in CML granulocytes compared to normal granulocytes and that the increased enzyme activity is specific for O-linked Gal beta 1----3GaINAc. This enzyme activity may be directly responsible for the abnormal membrane sialylation and pathophysiological behavior of these cells.
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PMID:Increased activity of a specific sialyltransferase in chronic myelogenous leukemia. 241 27

Basophils were isolated and propagated in large numbers from the blood of patients with chronic myelogenous leukemia. Propagation over 4-6 weeks of culture was dependent upon a growth factor(s) other than interleukin-2 obtained from a lectin-stimulated clone of the Jurkat cell line. Evidence that these basophils were dividing during culture included an increase in both the number of basophils and the histamine content of the cultures over time, as well as ultrastructural studies that demonstrated basophil cell division. The cells also had the capacity to be stimulated in an IgE-dependent manner characteristic of basophils. Cultured basophils passively sensitized with IgE underwent noncytotoxic degranulation after stimulation with specific antigen. Antigen-stimulated basophils released histamine, leukotrienes B4 and C4 and other 5-lipoxygenase products of arachidonic acid metabolism. Culture models such as this may permit the propagation and purification of sufficient numbers of basophils to allow biochemical and immunological analyses of basophil physiology.
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PMID:Propagation and characterization of human blood basophils. 245 92

Immunofluorescence and immunoblotting experiments, using a monoclonal antibody to the 13 kDa mammalian beta-galactoside-binding lectin have shown that human lymphocytes contain nuclear and cytoplasmic proteins of apparent molecular masses of 130, 80, 65 and 13 kDa that are antigenically related to the lectin and whose levels and patterns of expression change in association with transformation, or after stimulation with mitogens. These observations, together with the finding that the myeloid cell line K562 is also rich in the 130 kDa component, whereas the mature granulocytes of normal donors and of patients with chronic myeloid leukaemia are lacking in all of the immunoreactive forms, raise the possibility that this family of lectin-related proteins may be components of growth regulatory systems that are variously elicited in the transformed and stimulated cells.
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PMID:Transformation and growth related changes in levels of nuclear and cytoplasmic proteins antigenically related to mammalian beta-galactoside-binding lectin. 388 14

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

K-76 COONa is a derivative of a fungal product which blocks complement (C)-mediated lysis by combining with C5 and preventing its activation to C5b. K-76 COONa can also combine with Factor I and inhibit its ability to hydrolyze C3b to iC3b. The inclusion of K-76 COONa at concentrations similar to those which inhibit C lysis blocked both murine cytotoxic-T-lymphocyte (CTL)-mediated lysis (CML) and the lectin-stimulated proliferative response of murine and human T lymphocytes. A modified cation pulse procedure has been used to determine which phases of CML were most sensitive to the drug. K-76 COONa was inhibitory when it was added to CML prior to the early Mg+2-dependent binding phase, but was much less effective when it was added at any time after the formation of CTL-target conjugates. The principal effect of the drug on the proliferative response was also exerted during an early phase of the response. K-76 COONa did not appreciably decrease the production of T-cell growth factor (TCGF), but it did inhibit the induction of TCGF receptor expression by both functional criteria, i.e., induction of responsiveness to TCGF, and by morphological criteria, i.e., the expression of the Tac antigen. Later events, such as the TCGF-dependent proliferation of cycling T cells, were less sensitive to the drug. Evidence is discussed suggesting that molecules similar to Factor I and to C3 may be involved both in the early events of CML and of T-lymphocyte activation.
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PMID:The mechanism of cell-mediated cytotoxicity. IV. K-76 COONa, which inhibits the activity of Factor I and of C5, inhibits early events in cytotoxic T-lymphocyte-mediated cytolysis and in T-lymphocyte activation. 623 82

Normal human monocytes and macrophages, as well as in vitro human leukaemic promyelocytic cell line (HL-60) transformed into macrophage-like cells by 12-0-tetradecanoylphorbol-13-acetate (TPA) generate potent procoagulant activity (PCA) similar to tissue thromboplastin. In the present study, only mild PCA was detected in primary cultures of cells from the peripheral blood of patients with acute lymphatic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). After exposure to TPA, AML and CML cells assumed characteristics specific to monocytes and macrophages. Differentiation was associated with the generation of PCA. PCA was not found in ALL cells exposed to TPA. The PCA of TPA-induced macrophages derived from AML and CML cells resembled tissue thromboplastin and normal monocyte and macrophage PCA in several aspects: (a) accelerated clotting via the extrinsic coagulation pathway, (b) inhibition by concanavalin A and protection against lectin inhibition by methyl-alpha-D-mannopyranoside, (c) localization in the cell membrane. The capacity for PCA generation is additional evidence for the similarity between TPA-induced macrophages derived from AML and CML cells and normal human monocytes and macrophages.
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PMID:Generation of procoagulant activity (PCA) by macrophage-like cells derived from acute and chronic myeloid leukaemia cells in response to phorbol esters. 657 80

The fucose-binding lectin from Lotus tetragonolobus ( FBL -L) has been previously shown to bind specifically to normal cells of the myeloid and monocytic lineages. The purpose of this study was to explore the utility of fluoresceinated FBL -L as a leukemia differentiation marker in conjunction with a panel of other frequently used surface markers (Fc receptor, HLA-DR, OKM1, and antimonocyte antibody). FBL -L reacted with leukemic cells in 8/9 cases of clinically recognized acute myeloid leukemia, including myeloid blast crisis of chronic granulocytic leukemia, 3/3 cases of chronic phase chronic myelogenous leukemia, and in 2/7 cases of clinically undifferentiated acute leukemia. Correlations were noted between reactivity with FBL -L, and DR and Fc receptor expression. Among continuous cell lines, FBL -L bound with high intensity to a majority of HL-60 and U937 cells. The less well differentiated myeloblast cell lines, KG-1, KG1a , and HL-60 blast II, exhibited less FBL -L binding than HL-60 and U937. A moderate proportion of K562 cells exhibited low level binding of FBL -L. Several lymphoblastic cell lines exhibited a pattern of low intensity binding that was distinguishable from the high intensity binding pattern of the myeloblastic lines. FBL -L reactivity of U937 was enhanced by induction of differentiation with leukocyte conditioned medium, but not dimethylsulfoxide. Such treatments induced contrasting patterns of change of HL-60 and U937 when labeled with OKM1, alpha-Mono, and HLA-DR. These studies demonstrate the application of FBL -L to analysis and quantitation of myelomonocytic leukemic differentiation.
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PMID:Analysis of myelomonocytic leukemic differentiation by a cell surface marker panel including a fucose-binding lectin from Lotus tetragonolobus. 672 51

Human alloreactive cell lines were maintained in culture over prolonged periods of time using conditioned medium. Primed lymphocyte typing reactivity was observed in these T cell lines for only 1 mo, but these T cell lines have remained for more than 7 mo highly and specifically cytotoxic. Using as growth promoter an irradiated autologous feeder consisting of irradiated peripheral blood lymphocytes and the lectin leucoagglutinin, we have derived by limiting dilution cloning of in vitro primed allogeneic combinations, primary colonies (or primary clones) with monofunctional immune reactivities: either cytotoxic (the rarest observed) or PLT reactive (the majority of the colonies). Furthermore, each monofunctional primary colony when tested for PLT or CML reactivity on a panel of unrelated PBL, always showed a restricted specificity when compared to the original primed population. The PLT reactivity of each of the primary clones was short lasting in contrast to their growth potential. The CML reactivity of the primary clones, as for the T cell lines, was long lasting as was their growth potential.
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PMID:Expansion of human lymphocyte populations expressing specific immune reactivities. III. Specific colonies, either cytotoxic or proliferative, obtained from a population of responder cells primed in vitro. Preliminary immunogenetic analysis. 697 58


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