Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules CD58 and CD54 are involved in cell-cell interactions that are potentially important in the biology of acute leukemia (AL). Expression of these molecules was studied in 79 cases of adult AL including 50 cases of acute non-lymphoid leukemia (ANLL) and 29 cases of acute lymphoid leukemia (ALL) using an indirect immunofluorescence technique. CD58 was expressed in 45 +/- 26% of ANLL cells and 43 +/- 32% of ALL cells, and its expression did not correlate with any other marker. In ALL, the expression of CD58 was inversely correlated with the presence of a clinical tumoral syndrome (p = 0.0009), leucocytosis (p = 0.005), and the percent of peripheral blast cells (p = 0.001). The major finding in this study was the association between CD58 expression and prognosis. In ANLL, higher expression of CD58 was independently associated with higher CR rate (p = 0.04), longer overall survival (p = 0.02), and longer disease-free survival (p = 0.007). In ALL, higher expression of CD58 was associated with longer survival (p = 0.05). CD54 was expressed only on 17 +/- 16% of ANLL cells and 11 +/- 11% of ALL cells; its expression on ANLL was positively correlated with that of CD11 (p = 0.03), CD15 (p = 0.001) and CD34 (p = 0.01). CD54 expression did not correlate with clinical and hematologic characteristics. We conclude that the expression of adhesion molecule CD58, but not CD54, in AL is related to initial characteristics and evolution of the disease.
Leukemia 1992 Apr
PMID:Expression of surface adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3) in adult acute leukemia: relationship with initial characteristics and prognosis. 137 2

We review the role of adhesion molecule expression on malignant lymphoid cells as delineated by experimental studies and clinical observation. Adhesion molecules of the Ig superfamily, integrins, selectins, and the lymphocyte homing receptor CD44 mediate cell-to-cell and cell-to-extracellular matrix interactions. These molecules have been investigated with the aim (i) of defining certain biological features of the malignant cells, (ii) of providing a rationale to understand tumor organization, metastasis and organ specificity, and (iii) of detecting disease subsets and prognostic groups.
Leukemia 1992 Nov
PMID:Expression of adhesion molecules in lymphoproliferative disorders. 143 29

Adhesion receptors from the very late activation (VLA) (beta 1) integrin subfamily play a role in the cooperation of hematopoietic progenitors with bone marrow stroma, and the disregulated expression of these molecules, as evaluated by immunophenotyping, has been implicated in the acquisition of the malignant phenotype by hematopoietic cells. In the present study, Northern hybridization was used to determine the pattern of expression of transcripts for VLA subunits in: (i) leukemic blasts obtained from the peripheral blood of ten patients with acute myelogenous leukemia (AML) of different FAB subclasses; (ii) the human leukemic cell lines KG-1, HL-60, K-562, HEL and U-937; and (iii) normal hematopoietic cells. Most of the AML blasts and the cultured leukemic cells expressed mRNAs for the beta 1 and alpha 5 subunits (the only exception among the cell lines was KG-1 cells) and these transcripts were also found in normal bone marrow progenitors, peripheral blood mononuclear cells (PBMNC), and peripheral blood monocytes. While the alpha 4 transcript was detected in all cultured cells but K-562, and in normal circulating monocytes, it occurred in blasts from only two AML patients and was weakly expressed in mature PBMNC. No specific pattern of expression of beta 1, alpha 5, and alpha 4 transcripts could be related to cell differentiation or maturation in the AML blasts and leukemic cell lines tested. None of the primary AML blasts or cultured cells showed mRNA messages for alpha 2, alpha 3 or alpha 6 chains of the beta 1 integrins. The results suggest that, in some cases of AML, the malignant phenotype of leukemic blasts may be associated with down-regulated transcription of the alpha 4 integrin subunit.
Leukemia 1994 Sep
PMID:Expression of beta 1 integrin mRNAs in human leukemic blasts. 752 92

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.
Leukemia 1994 Feb
PMID:Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia. 830 57

Adhesion protein expression by acute myeloid leukaemia (AML) cells may affect bone marrow stromal localization and determine exposure of leukaemic cells to stromal derived myeloid growth factors. We have analysed the surface expression by myeloid leukaemic cells of proteins with known adhesive function and the ability of AML cells to adhere to bone marrow fibroblasts and the extracellular matrix proteins fibronectin and laminin. Cells from all six patients tested adhered to bone marrow fibroblast monolayers (mean binding 28.8 +/- 12.8%) and to purified fibronectin in five cases studied (mean binding 33.8 +/- 15.3%). Cells from four patients with AML also adhered to laminin (mean binding 20.9 +/- 4.0%). AML cells from the majority of patients with leukaemia at diagnosis or relapse expressed the ligand pair LFA-1 and ICAM-1, the CD2 ligand LFA-3, alpha and beta chains of the integrins VLA-4, VLA-5 and VLA-6, and the hyaluronate receptor CD44. Antibodies to CD11a, CD18, VLA-4 alpha, and VLA-5 alpha failed to inhibit binding of AML cells to bone marrow fibroblasts but anti-VLA-5 alpha antibodies inhibited AML cell binding to fibronectin by approximately 50%. The ability of AML cells to adhere to bone marrow fibroblasts and extracellular matrix proteins such as fibronectin and laminin may to help explain the capacity of AML cells to persist in the marrow during periods of apparent complete remission and to subsequently proliferate under the influence of locally secreted myeloid growth factors.
Leukemia 1993 Aug
PMID:Human acute myeloid leukaemia cells express adhesion proteins and bind to bone marrow fibroblast monolayers and extracellular matrix proteins. 835 Jun 18

Adhesion to bone marrow stroma is a key event in normal B lymphopoiesis, allowing exposure of B-cell progenitors to regulatory cytokines. In order to investigate whether similar processes are important in the proliferation of acute lymphoblastic leukaemia (ALL) cells of precursor-B type, the expression of various adhesion molecules was examined. By flow cytometry analysis, CD-44 and the integrins VLA-4 and VLA-5 were the most prominent. CD-44 and VLA-4 were expressed on all 18 cases of precursor-B ALL analysed, while VLA-5 was found on 15 of 18 cases. The integrin CD-11a was detected on 8 of 11 cases, while its ligand, CD-54, was present in 6/12. Other adhesion proteins such as beta 3 integrin, CD-56, CD-15, and Leu8 were not expressed to any significant extent. In view of the known binding of VLA-4 and VLA-5 to extracellular fibronectin (FN), the adhesion of leukaemic cells to FN was evaluated in a colorimetric assay. The precursor-B ALL cell lines REH and KM-3, and 7/15 cases of precursor-B ALL, showed detectable binding to FN. Binding to the other extracellular matrix proteins collagen type 1 and vitronectin was not observed, although two ALL cases showed some binding to laminin. The functional activity of the VLA-4 and VLA-5 molecules was examined using an inhibitory peptide and monoclonal antibodies. These studies indicated that ALL cells adhere to soluble fibronectin predominantly through the VLA-5 molecule (blockable with the PHM-2 antibody and a peptide containing the RGD sequence) although binding mediated by VLA-4 was also apparent in some experiments (blockable by a 40 kDa fragment containing the heparin-binding domain of FN and inhibitory antibodies). These results indicate that precursor-B ALL cells may adhere to marrow stroma through interaction of VLA-4 and VLA-5 with FN, although other mechanisms of adhesion may be important.
Leukemia 1993 Jan
PMID:Adhesion of precursor-B acute lymphoblastic leukaemia cells to bone marrow stromal proteins. 841 84

Cell surface-expressed proteoglycans mediate contacts to extracellular matrix (ECM). Human B lymphocytes produce a species of a proteochondroitin sulfate (CSPG) with an approximate molecular mass of 135-150 kDa. Using a monoclonal antibody (mAb) against B cell CSPG in flow cytometry we found that this CSPG is expressed on tumor cells of patients with CD19+ common acute lymphoblastic leukemia and on the corresponding cell lines Nalm-6, Reh and KM3. The CSPG is also present on hairy cell leukemia JOK-1 cells and weakly on the myeloma line U266. Concomitant with CSPG expression, Nalm-6 cells express the integrins alpha 5/beta 1 (CD49e/CD29) and alpha 6/beta 1 (CD49f/CD29), adhesion receptors for fibronectin and laminin, in contrast to the other two cell lines tested. Expression patterns of these adhesion receptors and CSPG were paralleled by strong adhesion of Nalm-6 to fibronectin and laminin. Adhesion of Nalm-6 to fibronectin was inhibited by the alpha 5-specific antibody SAM 1 by 80% whereas the alpha 6-specific antibody GoH3 reduced binding to laminin only by 20%. A possible involvement of surface-expressed CSPG in adhesion to ECM components was investigated by 24 h incubation of Nalm-6 cells with p-nitrophenyl-beta-D-xyloside, an inhibitor of proteoglycan glycosylation. By this treatment, both adhesion of Nalm-6 to laminin and expression of CSPG were reduced by 40-50%. Furthermore, addition of chondroitin-6-sulfate, a structural element of Nalm-6 CSPG, reduced adhesion of Nalm-6 to laminin by 60%. Chondroitin-4-sulfate, heparin and heparan sulfate did not effectively inhibit the adhesion process. These observations suggest that surface-expressed CSPG may be involved in binding of Nalm-6 cells to laminin and that the specific sulfation pattern of chondroitin-6-sulfate may be essential in this regard.
Leukemia 1996 Jun
PMID:Characterization of cell surface-expressed proteochondroitin sulfate of pre-B Nalm-6 cells and its possible role in laminin adhesion. 866 35

In order to elucidate the involvement of adhesion mechanisms in the process of megakaryocyte-dependent fibroblast growth, we applied BSA-coupled polymers of glucose, galactose, fucose, mannose, and several lectins (AAA, LCA, LTA, UEA-I) to cocultures of CD61 -positive (CD61+)/MACS-enriched megakaryocytes and human bone marrow fibroblasts. Fibroblast monocultures served as controls. After 6 days, glucose, as well as galactose-treated cultures showed a significant reduction of fibroblast growth in cocultures and fibroblast monocultures. In contrast, application of mannose caused no reducing effect on fibroblast numbers. Administration of fucose, AAA, LTA or UEA-I revealed a strong impairment of fibroblast growth in the megakaryocyte-fibroblast cocultures. Adhesion experiments using MACS-enriched, fluorescein-labelled megakaryocytes cultured in the presence of carbohydrates and lectins on a near-confluent layer of fibroblasts were additionally performed. Following fucose-BSA, alpha Fuc-1,2Gal beta-HSA or UEA-I treatment a significant reduction of megakaryocyte adhesion to the fibroblast layer could be observed. In the case of AAA a weak impairment of megakaryocyte adhesion could be noticed. Selective pretreatment of either fibroblasts or megakaryocytes with fucose-BSA or alpha Fuc-1,2Gal beta-HSA was consistent with the finding of a prominent involvement of fucosylated residues located on megakaryocytes in this interaction. In conclusion, our studies are in keeping with the assumption that fucosylated and fucose-binding structures are playing a key role in adhesion mechanisms between megakaryocytes and fibroblasts and thus influence significantly the megakaryocyte-dependent growth of bone marrow fibroblasts.
Leukemia 1996 Oct
PMID:Interactions between endogeneous lectins and fucosylated oligosaccharides in megakaryocyte-dependent fibroblast growth of the normal bone marrow. 884 95

Adhesion of normal colony-forming cells (CFC) to bone marrow (BM) stroma and the extracellular matrix (ECM) component fibronectin (FN) depends at least in part on the alpha4beta1 and alpha5beta1 integrins and the CD44 receptor. Aside from anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent adhesion of normal CFC is associated with inhibition of their proliferation. In contrast to normal CFC, chronic myelogenous leukemia (CML) Ph+ CFC adhere significantly less to either stroma or FN. CML Ph+ CFC proliferation is also not inhibited by coculture with stroma or FN. However, equal numbers of alpha4, alpha5, and beta1 integrins and CD44 are present on CML and normal CD34+ cells. We have previously demonstrated that beta1-dependent adhesion to and subsequent proliferation inhibition by FN can be restored when CML Ph+ CFC are incubated with the beta1 integrin activating antibody, 8A2, and demonstrated a role for the alpha5beta1 integrin in this phenomenon. Since the integrin alpha4beta1 and the proteoglycan form of CD44 may cooperate in establishing normal CFC adhesion to FN, we examined if treatment of CML Ph+ CFC with 8A2 also restores the cooperativity between beta1 integrins and CD44. We demonstrate that 8A2 induces adhesion of CML Ph+ CFC not only to intact FN but also to alpha4beta1, alpha5beta1, and proteoglycan binding fragments of FN. 8A2-induced adhesion to these fragments and peptides also results in a significant inhibition of the proliferation of CML Ph+ CFC. Addition of antibodies to either the alpha5, alpha4, or beta1 integrins, antibodies against the CD44 receptor, or removal of chondroitin sulfate glycosaminoglycans from the surface of CML CD34+ HLA-DR+ cells significantly reduced the 8A2-induced adhesion to and adhesion-mediated inhibition of proliferation by FN. These studies demonstrate that activation of beta1 integrins on CML Ph+ CFC not only results in upregulation of beta1 integrin-dependent adhesion and adhesion-mediated inhibition of proliferation, but also in the restoration of cooperation between beta1 integrins and CD44. These studies suggest that decreased beta1 integrin avidity may also affect the function of the proteoglycan adhesion receptor CD44, both of which may contribute to the abnormal circulation and expansion of malignant progenitors in CML.
Leukemia 1997 Jun
PMID:Activation of beta1 integrins on CML progenitors reveals cooperation between beta1 integrins and CD44 in the regulation of adhesion and proliferation. 917 35

Development of the hematopoietic lineages is partially under the control of hematopoietic receptors with tyrosine kinase activity (RTK). To compare the cellular functions of two of the class III RTK, FLT3 and KIT, a murine chimeric FMS/FLT3 (FF3) receptor was expressed ectopically using retroviral infection, in normal IL3-derived cultured mast cells. Stimulation of the chimeric receptor produced a full mitogenic signal and led to mast cell maturation, as occurs upon activation of the endogenous KIT receptor. When introduced into mast cells derived from KIT-deficient White spotting (W) mutant mice, the FF3 receptor bypassed their mitogenic defect. KIT activation induced a synergistic mitogenic activity in mast cells upon IL3 stimulation, whereas FF3 appeared to down-modulate the IL3 response. Adhesion to fibronectin was specifically associated with KIT signaling.
Leukemia 1998 Jul
PMID:Specific and common activities of the FLT3 and KIT tyrosine kinase receptors revealed by the use of cultured mast cells. 966 95


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