Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal and malignant plasma cells were investigated for the expression of seven cellular adhesion molecules by immunofluorescence microscopy. The antigens investigated were CD2 and its ligand, LFA-3 (CD58). LFA-1 alpha (CD11a) and LFA-1 beta (CD18) and their ligand ICAM-1 (CD54), H-CAM (lymphocyte homing receptor; CD44) and N-CAM (CD56). Marrow from 18 patients with myeloma, two with plasma cell leukaemia (PCL), four with monoclonal gammopathy of uncertain significance (MGUS) and 10 normal allogeneic bone marrow donors was studied. All plasma cells from normals and multiple myeloma patients were negative for CD2, CD11a and CD18. All normal and myeloma marrow plasma cells were positive for ICAM-1. 16/18 myeloma cases tested, and all other samples (normal, MGUS and PCL), contained plasma cells positive for H-CAM. Only one normal, but 12/16 myelomas tested were positive for N-CAM (P less than 0.02). One of four MGUS cases was moderately positive and one other weakly positive for N-CAM. Both PCLs were N-CAM negative. 12/18 myelomas were positive for LFA-3, but only two normals (P less than 0.05). All MGUS cases were negative for LFA-3, as was one PCL, the other being weakly positive. Three cases were negative for both adhesion molecules, three cases expressed only N-CAM or LFA-3 and 10 cases expressed both. LFA-3 and N-CAM are expressed significantly in myeloma rather than normal plasma cells. Cases of MGUS may express N-CAM but not, in this small series, LFA-3. Plasma cells in the peripheral blood (PCL) and plasma cell lines express little or no LFA-3 or N-CAM.
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PMID:Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells. 138 43

Human myeloma plasma cells had been considered to express few surface antigens until recently. The past two International Workshops on Leucocyte Differentiation Antigens have shown that myeloma cells can express a range of surface molecules, and it has become clear that many of these have adhesive functions. The identification of ICAM-1 (CD54) and H-CAM (CD44) on human plasma cells was the initial observation, and other antigens such as N-CAM (CD56) and LFA-3 (CD58) have been confirmed as features of malignant plasma cells in particular. The degree of expression of LFA-1 (CD11a) remains to be characterised fully. It seems probable that the loss of some adhesion structures may be associated with increased malignancy and plasma cell leukaemia. At the present time there are few studies relating to the function of these molecules, although homotypic adhesion appears to occur, and it is likely that such studies will shed light on the pathogenesis of myeloma.
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PMID:The role of adhesion molecules in multiple myeloma. 149 Jan 46

Interaction between immunocytes is essential for immune response to occur, and the part of it is mediated by cell adhesion mechanisms. However, little is known about the nature of homotypic adhesion between B cells. In order to investigate the mechanisms underlying the B cell adhesion, we tried to identify molecules involved in the adhesion process by raising monoclonal antibodies (mAb) against human B lymphoblastoid cell line WT46. One mAb. 33C4, reacted with all B cells, a part of T cells, and myeloma cells. Interestingly enough, 33C4 mAb induced aggregation of B cells, but not of T cells or other cells. Structural analysis showed that 33C4 molecule is a monomer of 45 kilodaltons with isoelectric point of 5.9. It is thus likely that 33C4 is a unique molecule involved in B cell aggregation and is clearly distinct from other cell adhesion molecules such as LFA-1, ICAM-1, and LFA-3. The mechanisms of aggregation induced by 33C4 mAb, however, remains to be determined.
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PMID:[Analysis of 33C4 monoclonal antibody associated with aggregation of human B lymphocytes]. 260 46

Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.
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PMID:Bone marrow of patients with active multiple myeloma: angiogenesis and plasma cell adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. 754 53

A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma.
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PMID:[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth]. 786 16

We observed a unique case of multiple myeloma that was transformed into plasma cell leukemia presenting with subcutaneous and soft tissue infiltrates. Subcutaneous and minor pelvic soft tissue plasmacytomas and the leukemic transformation were diagnosed in a 72-year-old woman after she had completed 9 months of chemotherapy for IgG kappa multiple myeloma. Immunophenotypic study revealed that leukemic cells in her peripheral blood were positive for ICAM-1 (CD54) but negative for LFA-1 alpha (CD11a) and LFA-1 beta (CD18), whereas infiltrating leukemic cells in the subcutaneous plasmacytoma of the left thigh were positive for LFA-1 alpha and LFA-1 beta but negative for ICAM-1. In addition, intermingling capillary endothelial cells were positive for ICAM-1. Extramedullary soft tissue plasmacytoma is uncommon in association with plasma cell tumors, and the exact mechanism of the development of plasmacytoma is not known. In the present case, however, the discordant expression of LFA-1/ICAM-1 adhesion molecules may have accounted for the distinct patterns of growth and the spread of the subcutaneous plasmacytoma through homing of the LFA-1 alpha+, LFA-1 beta+ leukemic cells to ICAM-1+ endothelial cells.
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PMID:Discordant LFA-1/ICAM-1 expression in a case of secondary plasma cell leukemia associated with subcutaneous plasmacytoma. 809 44

In a previous study the expression of the adhesion molecule LFA-1 on tumour cells in patients suffering from multiple myeloma (MM) was correlated with growth of the malignant plasma cells in vivo. Here we describe a novel in vitro flow cytometric adhesion assay (FCAA) which, based on scatter and fluorescence properties, was used to analyse the contribution of the LFA-1/intercellular adhesion molecule-1 (ICAM-1) adhesion pathway in the binding of bone marrow (BM)-derived LFA-1-positive primary tumour cells of patients with MM to interferon-gamma (IFN-gamma)-activated, ICAM-1-positive, human venous umbilical endothelial cells (huVEC) in vitro. To validate the FCAA, cells from different myeloma cell lines were labelled with the fluorescent dye CFDA or stained for CD38 expression, and LFA-1-mediated adhesion to IFN-gamma-activated endothelial cells was quantified. Results obtained with the FCAA were compared with a conventional adhesion assay employing 51Cr-labelled cells. Statistical analysis revealed that both assays gave similar results. This allowed analysis of the contribution of LFA-1 to the adhesive potential of malignant plasma cells in bone marrow mononuclear cells (BMMC) from MM patients to IFN-gamma-activated endothelial cells. The results prove that LFA-1 expressed on bone marrow-derived plasma cells from MM patients can be used for cellular adhesion to ICAM-1 expressed on adherent growing cells, and are suggestive for a role of the LFA-1/ICAM-1 adhesion pathway in the pathophysiology of MM. The FCAA described in this study is a generally applicable assay, allowing analysis of the interaction of distinct subpopulations with in vitro grown adherent cells of different origin.
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PMID:A novel flow cytometric assay for the quantification of adhesion of subsets within a heterogeneous cell population; analysis of lymphocyte function-associated antigen-1 (LFA-1)-mediated binding of bone marrow-derived primary tumour cells of patients with multiple myeloma. 810 18

We and others have shown that some freshly isolated multiple myeloma (MM) cells and derived cell lines express interleukin 6 (IL-6) receptors and proliferate in vitro in response to IL-6; a subset of MM cells also expresses IL-6 mRNA, is intracytoplasmic IL-6 positive and secretes IL-6. We have shown that MM cells express the cell surface adhesion molecules CD29/CDw49d(VLA-4), CD18/CD11a(LFA-1) and CD44, and may localize to marrow via specific adherence to both extracellular matrix proteins and to bone marrow stromal cells (BMSCs). MM cell adhesion triggers IL-6 secretion by normal and MM BMSCs and related IL-6-mediated tumor cell growth. Our attempts to block MM cell adhesion to BMSC-induced IL-6 secretion by using antibodies to CD29/CDw49d, CD18/11a, and/or CD44 demonstrated minimal effects, suggesting that another ligand-receptor interaction triggers IL-6 secretion when MM cells and BMSCs are juxtaposed. Both MM cells and BMSCs express CD40. Triggering of MM cells and BMSCs via CD40 upregulates IL-6 secretion in both MM cells and MM-derived cell lines, as well as BMSCs and BMSC lines, suggesting the possibility of both autocrine and paracrine MM cell growth triggered via CD40. Finally, experiments using the LP 101 BMSC line transiently transfected with IL-6 promoter fragments linked to chloramphenicol acetyltransferase reporter gene demonstrate that adhesion of MM cells induces IL-6 gene transcription in BMSCs, which is conferred via the NF-kappa B binding motif.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of interleukin 6 in multiple myeloma and bone marrow stromal cells. 852 May 9

The authors present information on the presence of adhesive proteins on membranes of myeloma and precursor cells isolated from bone marrow and blood from a group of 33 patients examined by fluorescent flow cytometry. They also compare the density of integrins (CD29, CD49e, CD41, CD51 and CD61) and adhesive proteins from the group of "homing" receptors (CD44) and IgG "superfamily" (LFA-1, LFA-3, ICAM-1, N-CAM) and their changes after a single oral dose of a mixture of proteolytic enzymes (Wobe Mugos, Wobenzym, MUCOS Pharma, FRG). The authors observed a significant drop of CD29, CD54 (ICAM-1), CD58 (LFA-3) after Wobe Mugos, CD49, CD51, CD58 after Wobenzyme. The insignificant decline of density of CD44 on cells, as well as of the soluble receptor of CD44 after oral administration of proteolytic enzymes in serum, incl. the mentioned changes of integrins and other adhesive proteins, indicate the importance of enzyme preparations in the supporting treatment of malignant processes.
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PMID:[Density of adhesive proteins after oral administration of proteolytic enzymes in multiple myeloma]. 860 Jun 53

We investigated the expression of adhesion molecules including LFA-1 alpha (CD11a), Mac-1 (CD11b), LFA-1 beta (CD18), VLA-beta 1 (CD29), H-CAM (CD44), VLA-4 (CD49d), VLA-5 (CD49e), ICAM-1 (CD54), N-CAM (CD56), LFA-3 (CD58), VNR-beta (CD61), and LECAM-1 (CD62L) on fresh myeloma cells and human myeloma cell lines. By two-color flow cytometric analysis with anti-CD38 antibody, we demonstrated that myeloma cells were located in the strongly CD38-positive (CD38++) fractions. Fresh myeloma cells were obtained from 28 patients with multiple myeloma (MM) and 3 patients with plasma cell leukemia (PCL). All myeloma cells expressed VLA-4 on their surface. Most of the myeloma cells also expressed VLA-5, ICAM-1, and LFA-3, H-CAM was strongly expressed in 3 cases of PCL and 2 cases of aggressive myeloma, and moderately expressed in other MMs. N-CAM was expressed in 68% of MMs, but none of the 3 PCLs. LFA-1 was expressed in two cases of aggressive myeloma, but not expressed in other non-aggressive myelomas. Most of the myeloma cells did not express Mac-1, VNR-beta, or LECAM-1. These results suggest that VLA-4, VLA-5, ICAM-1, LFA-3, and H-CAM are involved in cellular interaction and migration in MM, and that the expression of N-CAM and LFA-1 varies with disease activity in MM.
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PMID:Expression of adhesion molecules on myeloma cells. 879 90


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