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)

The aim of the present study was to evaluate the surface membrane glycoproteins of pseudo-Pelger granulocytes in six patients suffering from chronic myeloid leukaemia (CML). We studied the functional and immunochemical activities of five monoclonal antibodies (MoAb) minimally reactive with integrin familial antigens of pseudo-Pelger granulocytes. The study conducted with cytofluorimetric and immunological alkaline phosphatase anti-alkaline phosphatase (APAAP) analysis showed a decreased expression of CD11b/CD18 detected by antibodies OKM1, 60.1 and 60.3 (P less than 0.001). Lymphocyte function associated antigen (LFA-1) was expressed in normal amounts in pseudo-Pelger granulocytes. There was decreased expression of CD11b/CD18 in pseudo-Pelger granulocytes with respect to controls (P less than 0.001) after stimulation with formyl-met-leu-phe (FMLP). We conclude that acquired pseudo-Pelger granulocyte dysfunction may be correlated to decrease of surface glycoprotein expression of CD11b/CD18.
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PMID:Surface expression of CD11b/CD18 of pseudo-Pelger granulocytes in chronic myeloid leukaemia. 198 28

The receptor on human neutrophils (polymorphonuclear leukocytes) that mediates cellular adherence consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000). We isolated a cDNA clone for the human neutrophil alpha M subunit by screening a lambda gt 11 cDNA library made from chronic myelogenous leukemia neutrophils by using an affinity-purified rabbit polyclonal antibody directed against the alpha M subunit. We used this cDNA clone to obtain additional clones from cDNA libraries made from differentiated HL-60 promyelocytic leukemia cells. Together these cDNAs constitute the complete 1137-amino acid sequence for the mature human alpha M subunit protein. The deduced amino acid sequence indicates the presence of an extensive extracellular domain with three putative metal-binding regions, (i) an amino acid region that is homologous to the A domain of von Willebrand factor, (ii) a 26-amino acid hydrophobic sequence that is a potential transmembrane domain, and (iii) a 19-amino acid cytoplasmic region. The amino acid sequence for the human neutrophil alpha M subunit contains regions that are closely related to amino acid sequences of adhesion receptors belonging to the integrin family.
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PMID:cDNA sequence for the alpha M subunit of the human neutrophil adherence receptor indicates homology to integrin alpha subunits. 256 62

Using a cDNA clone for the beta-subunit of the receptor on human leukocytes that mediates cellular adherence (CD18), we investigated the lineage specificity of beta-subunit mRNA expression in human hematopoietic cells. Relatively high levels of the beta-subunit mRNA transcript were detected in mature peripheral blood leukocytes, including granulocytes and both resting and PHA-activated T lymphocytes. In contrast, relatively low levels of this transcript were observed in EBV-transformed B cells, in the immature Jurkat T cell line, and in chronic myelogenous leukemia myeloblasts and lymphoblasts. The beta-transcript was undetectable in the K562 chronic myelogenous leukemia blast crisis cell line with erythroblastic characteristics and in cultured skin fibroblasts. Two acute myeloid leukemia samples displayed unusually high levels of this transcript, comparable to levels observed in mature PBL. beta-subunit mRNA expression appeared to be primarily confined to leukocytes. In all cells examined the levels of surface beta-Ag expression paralleled levels of beta-mRNA.
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PMID:Expression of the beta-subunit of the human leukocyte adherence receptor depends upon cell type and stage of differentiation. 290 71

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.
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PMID:Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells. 759 66

Changes in the intracellular Ca2+ levels of human large granular lymphocytes (LGL), loaded with the fluorescent Ca2+ indicator fura-2, have been studied upon addition of human chronic myelogenous leukemia K562 cells. The measurements, analyzed at the single-cell level using image analysis, indicate a rapid Ca2+ mobilization in the effector cell upon interaction with its target cell. This mobilization appeared to be localized to an area within the effector cell that was in physical contact with target cells. The LGL responded with different kinetics in a transient manner and about 19% of them could undergo two or more responses. Data obtained from experiments performed with anti-CD16- and anti-CD18-pretreated LGL in the presence of target cells indicate that the CD16 and CD18 molecules are not likely to be the triggers of the Ca2+ response, although they might participate in the recognition of the target cell.
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PMID:Rapid Ca2+ mobilization in single LGL cells upon interaction with K562 target cells--role of the CD18 and CD16 molecules. 767 26

The CD11b/CD18 leukocyte integrin molecule mediates diverse neutrophil adherence-related functions, including cell:cell and cell:extracellular matrix attachments. To study the individual role of this leukocyte integrin in cell adherence in hematopoietic cells, we expressed the CD11b/CD18 complex on the surface of K562 cells, a cell line derived from an individual with chronic myelogenous leukemia in blast crisis. We used an amphotrophic retroviral vector designated LCD18SN, harboring the complete coding sequence for the CD18 subunit, to transfer the CD18 cDNA into K562 cells and select stable cell lines. The CD11b subunit in the expression plasmid pREP4 was transfected into these K562/CD18 cells by electroporation and stable cell clones were selected. These K562 cells possessed RNA and intracellular protein for each subunit, and they expressed the CD11b/CD18 heterodimer on the cell surface. When CD11b/CD18 expressing K562 cells were stimulated with phorbol myristate acetate (50 ng/mL) for 24 to 48 hours, these K562 cells formed dense cell:cell aggregates. This homotypic aggregation required both activation of the CD11b/CD18 complex and the induction of the counter-receptor for CD11b/CD18 on the conjugate cell. This cell line will (1) enable the structure-function relationships between cell activation and homotypic adherence to be assessed, (2) provide the opportunity to identify accessory molecules required for activation of the CD11b/CD18 complex, and (3) facilitate the identification of novel ligands for the CD11b/CD18 complex.
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PMID:Transfected leukocyte integrin CD11b/CD18 (Mac-1) mediates phorbol ester-activated, homotypic cell:cell adherence in the K562 cell line. 840 Mar

Morphologically mature granulocytes from patients with chronic myeloid leukemia exhibit a defect in receptor mediated endocytosis of FITC-conjugated heat-aggregated IgG. In our earlier studies, we have shown that transcripts for Fc gammaRII and Fc gammaRIII are lowered in CML granulocytes, while no such trend was seen for CD11b, CD18 and actin, the other molecules involved in this process. We have also shown by flow cytometry that the number of granulocytes expressing the Fc receptors on their surface is lowered in CML patients. In this report, we show that the lowered steady state level of the mRNA for the Fc receptors is due to their faster degradation and not due to any defect in transcription. A study of the expression of mRNA for Fc gammaRIII in morphologically mature CML granulocytes by in situ hybridization showed that there is heterogeneity in the expression of this receptor, with some cells positive for the message and some not. These results suggest that the Fc gammaRIII transcript reaches a stable RNA pool in only some of the granulocytes, whereas in the rest of the cells, it is probably degraded after it is transcribed and is therefore not detected. The Fc gammaRIII is probably one of the first antigens to be lost from the leukemic granulocyte surface during the transition of the disease from the chronic phase to the accelerated phase and finally to the blast crisis.
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PMID:Heterogeneity in the expression of Fc gammaRIII in morphologically mature granulocytes from patients with chronic myeloid leukemia. 911 Nov 67

An 8-year-old male neutered Labrador Retriever was referred to the University of Wisconsin Veterinary Medical Teaching Hospital with a presumptive diagnosis of leukemia. Hematologic abnormalities included normal neutrophil count with a left shift, monocytosis, eosinophilia, thrombocytopenia, and circulating immature mononuclear cells. Bone marrow was effaced by immature hematopoietic cells of various morphologic appearances. In addition, large multinucleated cells were observed frequently. Flow cytometric analysis of nucleated cells in blood revealed 34% CD34(+) cells, consistent with acute leukemia. By immunocytochemical analysis of cells in blood and bone marrow, some mononuclear cells expressed CD18, myeloperoxidase, and CD11b, indicating myeloid origin; some, but not all, large multinucleated cells expressed CD117 and CD42b, the latter supporting megakaryocytic lineage. The diagnosis was acute myeloblastic leukemia without maturation (AML-M1). To identify genetic aberrations associated with this malignancy, cells from formalin-fixed paraffin-embedded bone marrow were analyzed cytogenetically by multicolor fluorescence in situ hybridization (FISH). Co-localization of bacterial artificial chromosome (BAC) containing BCR and ABL was evident in 32% of cells. This confirmed the presence of the canine BCR-ABL translocation or Raleigh chromosome. In people, the analogous translocation or Philadelphia chromosome is characteristic of chronic myelogenous leukemia (CML) and is rarely reported in AML. BCR-ABL translocation also has been identified in dogs with CML; however, to our knowledge this is the first report of AML with a BCR-ABL translocation in a domestic animal.
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PMID:Acute myeloblastic leukemia with associated BCR-ABL translocation in a dog. 2274 55

Twenty patients with self-sustaining hematopoiesis were evaluated for neutrophil functions and bone marrow histology 7 to 34 months after bone marrow transplantation (BMT) (7 allogeneic, 13 autologous) performed for acute leukemia in complete remission (11 patients), Hodgkin's lymphoma (2 patients), chronic myeloid leukemia (6 patients) or severe aplastic anemia (1 patient). The chemotactic response toward zymosan-treated serum was severely depressed (<35% of normal) in peripheral neutrophils of 11 patients (2 allogeneic and 9 autologous BMT) and moderately defective (35-70% of normal) in 5 others (2 allogeneic and 3 autologous BMT). On the other hand, phagocytic activity, activation of the metabolic burst and surface expression of CD11/CD18 molecules were within normal limits or moderately increased. The chemotactic defect was independent of age, sex, conditioning regimen and the time period after marrow infusion. The incidence of defective chemotaxis was much greater in patients receiving an autologous BMT (92% of the patients) than in those who had an allogeneic BMT (57% of the patients). Simultaneous bone marrow biopsy studies showed significant stromal alterations in most of our patients; since the bone marrow microenvironment plays an essential role in the process of blood cell formation and release, these observations suggest that defective neutrophil chemotaxis may well serve as a marker of abnormal post-transplant hematopoiesis.
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PMID:Abnormal Neutrophil Chemotaxis after Successful Bone Marrow Transplantation. 2746 65

A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets. Bone marrow examination revealed marked myeloid and megakaryocytic hyperplasia with 7% blasts, erythroid hypoplasia, and trilineage dysplasia. Flow cytometric analysis confirmed that bone marrow cells were mostly of neutrophil lineage, with reduced expression of common leukocyte antigens (CD45, CD18) and neutrophil-specific antigen. Bone marrow cells were cytogenetically analyzed for the breakpoint cluster region-Abelson oncogene using multicolor fluorescent in situ hybridization. The genetic aberration was present in 7% of cells, which was a negative result (>10% of cells is considered positive). Euthanasia was elected. Histologic examination showed extensive infiltration of multiple organs by neoplastic myeloid cells, with effacement of lymph node and splenic architecture. The final diagnosis was atypical chronic myeloid leukemia (aCML), an uncommon myeloproliferative disorder with features of myelodysplastic syndromes (dysplasia) and chronic leukemia (neutrophilic leukocytosis with <20% marrow blasts, extramedullary infiltrates). The trilineage dysplasia, lack of monocytosis, and supporting cytogenetics distinguish aCML from CML, chronic neutrophilic leukemia, and chronic myelomonocytic leukemia.
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PMID:Atypical chronic myeloid leukemia in a German Shepherd Dog. 2820 62


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