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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent immunophenotypic analysis has shown that the heterogeneous expression of the adhesion molecule VLA-5 classifies myeloma cells into VLA-5+ mature and VLA-5- immature subpopulations. To further clarify the two myeloma subpopulations, we generated a monoclonal antibody, MPC-1, by immunizing mice with an adherent human myeloma cell line, KMS-5. The MPC-1 antibody recognized a 48-Kd surface antigen on KMS-5 but not on U-266, a nonadherent human myeloma cell line. Specificity characterization showed that MPC-1 antigen was expressed on mature myeloma cells, normal plasma cells, and mature B cells, whereas pre-B cells and germinal center B cells lacked its expression. Monocytes and a human bone marrow stromal cell line, KM102, also expressed this antigen. Two subclones of MPC-1+ VLA-5+ (KMS-5Ad) and MPC-1-VLA-5+ (KMS-5NAd) were separated from the KMS-5 cell line. The KMS-5NAd adhered to KM102 more tightly than did the KMS-5NAd, and the U-266 (MPC-1-VLA-5-) displayed almost no adherence to the KM102. The adhesion of the KMS-5Ad was partially inhibited by the MPC-1 antibody. These results, taken together, suggest that the MPC-1 antigen serves as a differentiation marker for B-lineage cells, including plasma cells, and may function as an adhesion molecule involved in the interaction of mature myeloma cells with bone marrow stromal cells.
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PMID:Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible involvement of MPC-1 antigen in the adhesion of mature myeloma cells to bone marrow stromal cells. 826 Jul 9

With regard to the expression of adhesion molecules, human myeloma cells freshly isolated from bone marrow were heterogeneous. By two-color analysis with anti-VLA-5 antibody (PE staining) and FITC-labeled anti-CD38 antibody, we found all myeloma cells located at CD38-strong positive (CD38++) fraction and identified two subpopulations among these myeloma cells: CD38++ VLA-5-(VLA-5-) myeloma cells and CD38++ VLA-5+ (VLA-5+) myeloma cells. To clarify the biologic character of these two subpopulations, the morphology, in vitro proliferative activity and in vitro M-protein secretion were examined in each fraction isolated by the purification procedure or a cell sorter. Morphologic examination showed that VLA-5- myeloma cells were mostly immature or plasmablastic and VLA-5+ cells were mature myeloma cells. Furthermore, VLA-5- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL-6), a growth factor for myeloma cells, while VLA-5+ myeloma cells showed very low uptakes of 3H-thymidine and no responses to IL-6 but secreted higher amounts of M-protein (immunoglobulin) in vitro significantly. Therefore, we could clarify here heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA-5, one of integrin adhesion molecules; VLA-5- myeloma cells were proliferative immature cells and VLA-5+ cells were mature myeloma cells.
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PMID:Identification of immature and mature myeloma cells in the bone marrow of human myelomas. 832 11

Multiple myeloma represents a B cell malignancy characterized by a monoclonal proliferation of plasma cells. A striking feature of the disease is the tendency of the malignant plasma cells to affect mainly the bone marrow environment and to invade the peripheral blood only in the terminal stage. The growth of myeloma plasma cells is believed to be regulated by a functional interplay between the tumor cells and the bone marrow stroma, involving the action of various cytokines. This growth control is most probably mediated by close cellular contact of the myeloma cells and marrow stromal components. Therefore it can be assumed that myeloma plasma cells possess the ability to interact with the bone marrow stroma. Until now the adhesive mechanisms that may underlie this interaction, remain undetermined. We investigated the expression of several adhesion molecules on bone marrow plasma cells in myeloma patients and normal controls. Normal as well as malignant plasma cells were found to be strongly positive for the intercellular adhesion molecule ICAM-1, the fibronectin receptor VLA-4 and the lymphocyte homing receptor CD44. In addition, a much weaker expression of the second fibronectin receptor VLA-5, the laminin receptor VLA-6 and the vitronectin receptor CD51 was demonstrated. In contrast to normal plasma cells, myeloma cells can also express the neural cell adhesion molecule N-CAM. In this report we discuss the possible role of adhesion molecules in the pathogenesis and clinical evolution of multiple myeloma.
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PMID:The involvement of adhesion molecules in the biology of multiple myeloma. 833 50

Using two-colour phenotypic analysis with anti-CD38 antibody, human myeloma cells can be classified into VLA-5- immature and VLA-5+ mature cells. We examined the relationship between variations of these subpopulations and clinical responses during treatment in multiple myeloma (MM). 39 patients with MM were treated with combined chemotherapy. First estimation of clinical responses after induction therapy showed that early clinical responses were correlated with the percentage of immature myeloma cells present after induction therapy (P < 0.01), not at diagnosis. After three courses of cyclic maintenance therapy, immature myeloma cells significantly decreased in proportion along with a decrease in total myeloma cells in maintained or more responsive cases (P < 0.01). On the other hand, immature myeloma cells were still found in high proportions in nonresponsive cases with no change (NC) or minor response (MR) (P < 0.01). Furthermore, in relapsing cases from partial response (PR) or progressive disease (PD) from nonresponsive cases, immature myeloma cells increased markedly. Therefore these results show that high proportions of VLA-5- immature myeloma cells remaining after induction therapy and during maintenance therapy correlate well with a declining clinical course of MM during maintenance therapy.
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PMID:High proportions of VLA-5- immature myeloma cells correlated well with poor response to treatment in multiple myeloma. 854 30

Here, we propose a new phenotypic classification of bone marrow plasmacytosis. By 2-color phenotypic analysis with FITC anti-CD38 and PE anti-CD19, -CD56, -VLA-5 or MPC-1 antibody, plasma cells are easily identified on the histogram, even though no more than 1% of plasma cells are found in the bone marrow. Hence, plasma cells are phenotypically classified into polyclonal (reactive) (CD19+CD56-) or monoclonal (neoplastic) plasma cells (mostly CD19-CD56+), and furthermore immature (VLA-5-MPC-1-), intermediate (VLA-5-MPC-1+) and mature plasma cells (VLA-5+MPC-1+). According to these findings, plasmacytosis in the bone marrow can be classified into polyclonal marrow plasmacytosis (POMP) and monoclonal marrow plasmacytosis (MOMP) states. The MOMP state is further subclassified into MOMP-1 and MOMP-2, MOMP-3 and MOMP-4; MOMP-1 is defined by co-existence of monoclonal plasma cells and polyclonal plasma cells, and MOMP-2 to MOMP-4 are dependent on increased proportions of VLA-5-MPC-1- immature myeloma (plasma) cells. We found that the cases of benign monoclonal gammopathy (BMG) according to the conventional classification were in the MOMP-1 state, and myelomas could be classified into the MOMP-2 to MOMP-4 state. Subclassification of the MOMP state may be useful in determining the prognosis of myelomas, where an increase in immature myeloma cells is reported to correlate well with their aggravation during the clinical courses. Therefore, this new phenotypic classification of bone marrow plasmacytosis (POMP and MOMP-1 to MOMP-4) will contribute to differential diagnosis and understanding of therapeutic responses and prognosis in myelomas.
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PMID:A new phenotypic classification of bone marrow plasmacytosis. 854 6

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.
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PMID:Identification of early plasma cells in peripheral blood and their clinical significance. 856 94

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

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.
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PMID:Characterization of cell surface-expressed proteochondroitin sulfate of pre-B Nalm-6 cells and its possible role in laminin adhesion. 866 35

The biology of normal plasma cells and the pathophysiology of human multiple myeloma remain poorly understood. Functional assays are scarce and at present cell phenotyping is providing the most information about how human plasma cells may behave. Three different types of human plasma cells: normal, fresh neoplastic myeloma cells and plasma cell lines, have been studied for their reactivity with antibodies to the beta-1 integrins (Very Late Antigens; VLAs), including a panel obtained from the Vth International Workshop on Leucocyte Differentiation Antigens. Most plasma cell targets express VLA-4 (CD49d positive) and the common beta chain recognized by CD29. CD49e (VLA-5) was occasionally positive. Other VLAs were not usually expressed. These data suggest the wide use by plasma cells of VLA-4, possibly as a ligand with fibronectin and high endothelial venules (HEV). Of other adhesion structures expressed by plasma cells, only CD44 is seen as frequently, and this is also a HEV ligand.
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PMID:Very late antigen (VLA) expression by normal and neoplastic human plasma cells; including an assessment of antibodies submitted to the Vth International Workshop on Leucocyte Differentiation Antigens using human myeloma cell lines. 879 96

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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