UMLS:C0026764 - FACTA Search

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

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

In previous work, we reported the development of the B9/BMI syngeneic murine bone marrow metastasis model. Interleukin (IL)-6-dependent, IL-I-producing B9/BMI cells, which preferentially home to and colonise the vertebral and femoral marrow after i.v. injection, exhibit striking similarity in cell surface phenotype to human myeloma cells, especially the expression of 3 adhesion molecules, CD44, VLA-4 and ICAM-I. Because the haematopoietic microenvironment consists of different cell types, such as endothelial cells, fibroblasts, adipocytes and macrophages, we investigated the functional significance of these adhesion molecules in heterotypic binding assays between B9/BMI cells and a newly established bone marrow-derived endothelial cell line (BMEC), a fibroblastoid pre-adipocyte cell line (BMS2.2) and primary bone marrow-derived macrophages. B9/BMI cells adhered well to all stromal elements: a combination of monoclonal antibodies (MAbs) against CD44 and VLA-4 significantly inhibited the adherence of B9/BMI cells to BMEC and BMS2.2 cells, whereas binding of B9/BMI cells to macrophages was partially blocked with an anti-ICAM-I MAb. Our results implicate multiple recognition mechanisms, including those involving CD44, VLA-4 and ICAM-I, in the retention of B9/BMI cells in the bone marrow.
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PMID:Adhesion molecules involved in the binding of murine myeloma cells to bone marrow stromal elements. 884 41

CD44 variant isoforms (CD44v) are generated by alternative splicing of the nuclear RNA resulting in the expression of additional protein domains in the extracellular region of the CD44 standard molecule (CD44s). In multiple myeloma (MM), CD44 mediates binding of tumor cells to stroma and regulates interleukin-6 production. To evaluate the role of CD44v isoforms in MM, CD44v expression was analyzed by immunohistochemical staining of 64 bone marrow biopsies from 38 MM patients. Expression of variant isoforms containing the 9v domain was observed in 36% of cases and was associated with an advanced stage (P < .02; n = 61), a progressive disease (P < .001; n = 61), and a shorter overall survival (P < .02; n = 36). In contrast, 3v, 4v, 6v, or 10v isoforms were detected only in a small percentage of the patients. To analyze the exon composition in RNA-transcripts, reverse transcriptase polymerase chain reaction analyses followed by Southern hybridization with exon-specific probes were performed in fluorescence-activated cell sorted myeloma plasma cells. Tumors expressing the 9v domain showed complex, 9v-containing transcripts in combinations with the 3v, 7v, 8v, and 10v exons. Identical transcripts were detected in several myeloma cell lines and in a Ki-1 B-immunoblastic lymphoma. Similar to high-grade non-Hodgkin's lymphoma and gastric and renal cell carcinoma, overexpression of 9v-containing isoforms in MM is related to an unfavorable clinical presentation and represents a new prognostic parameter.
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PMID:Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. 887 9

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.
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PMID:Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression. 896 Jan 9

The neoplastic plasma cells of multiple myeloma differ from normal plasma cells and other B-cell malignancies by an almost exclusive homing to the bone marrow microenvironment which clearly provides the appropriate support, both physical and cytokine, to mediate clonal proliferation and terminal differentiation. Cellular adhesion molecules are involved in the homing of malignant plasma cells to the bone marrow, the production of growth factors and the recirculation of these tumour cells in the advanced stages of disease. Neoplastic plasma cells express H-CAM (CD44), VLA-4 (CD49d/CD29), ICAM-1 (CD54), N-CAM (CD56) and LFA-3 (CD58). In addition VLA-5 (CD49e/CD29) expression seems to be related to cells with less proliferative potential and more potential for paraprotein production. In addition there are fundamental changes in the bone marrow stroma of patients with multiple myeloma including altered composition of the extracellular matrix, increased growth capability of the cellular elements and increased synthesis of interleukin-6 and interleukin-3, which are features postulated to localise and promote growth of the circulating neoplastic progenitors in the bone marrow. However, the evidence to date does not fully explain the inter-relationship of the clonal B cells and the bone marrow stroma in patients with myeloma, including factors which trigger and facilitate the extravasation and recirculation of neoplastic plasma cells as seen in advanced disease.
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PMID:The role of adhesion molecules in multiple myeloma. 898 Jun 13

We have earlier described the presence of phenotypically unusual monoclonal B cells within the peripheral blood of multiple myeloma (MM) patients. To determine the biological properties of these B cells as compared to B cells from normal donors, we investigated the potential of CD19+ MM blood B cells to adhere to endothelial cell and bone marrow (BM)-fibroblast monolayers. We find that 30-60% of freshly isolated CD19+ MM blood B cells adhere to endothelial cell monolayers, and 50-80% adhere to BM fibroblast monolayers. The adhesion of MM blood B cells to either monolayer was not increased by in vitro activation, suggesting that these cells were activated in vivo. In contrast, fewer than 10% of CD19+ B cells from peripheral blood of normal donors adhered. Function-blocking monoclonal antibodies (mAbs) were used to determine which adhesion receptors were involved in CD19+ MM blood B cell interaction with BM fibroblasts. mAbs against very late antigen 4, the beta7-integrin subunit, and CD44, but not mAbs against very late antigen 5 and beta1, inhibited adhesion 61, 50, and 30%, respectively. The lack of inhibition with mAbs against beta1 implicates alpha4beta7 but not alpha4beta1 in adhesion of CD19+ MM blood B cells. To determine the alpha4beta7 ligand that mediated MM blood B cell adhesion, mAbs against vascular cellular adhesion molecule 1 and fibronectin, as well as CS1 and RGD peptides, were used as inhibitors. These were unable to reduce the adhesion of CD19+ MM blood B cells to BM fibroblasts, suggesting that fibronectin and vascular cellular adhesion molecule 1 are not involved in adhesion. Also, adhesion of MM blood B cells to mucosal addressin cell adhesion molecule 1-transfected Chinese hamster ovary cells was not enhanced compared to control-transfected Chinese hamster ovary cells, suggesting that mucosal addressin cell adhesion molecule 1 was not promoting adhesion of these cells. These data implicate CD44:HA interactions, as well as alpha4beta7 and an as yet unidentified ligand in the adhesion of in vivo activated MM blood B cell adhesion to BM fibroblasts. The adhesion properties of MM CD19+ B cells distinguishes them from normal B cells. Although the malignant status of these cells is as yet undefined, their adhesion properties implicate MM blood B cells in migratory spread of the disease.
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PMID:Adhesion of multiple myeloma peripheral blood B cells to bone marrow fibroblasts: a requirement for CD44 and alpha4beta7. 904 Nov 97

A human monoclonal antibody (mAb), designated mNKES, was generated by fusing B cells isolated from an enlarged cervical lymph node of a patient with a carotid body tumor (CBT), with human myeloma cell line KR-12 (6TG). The reactivity of mNKES was tested by the indirect immunofluorescence method. The antigen defined by mNKES was expressed on Burkitt's lymphoma cell lines Raji, Daudi, and Ramos and on B lymphoblastoid cell line IM-9. In addition, mNKES reacted with T cells stimulated with recombinant interleukin-2 (rIL-2) obtained from normal healthy donors. However, mNKES did not react with normal resting human T, B, or adherent cells (monocytes/macrophages). When the reactivity of mNKES and mouse mAbs recognizing the human adhesion-associated antigen (CD10, CD11a, CD11b, CD11c, CD14, CD16, CD18, CD23, CD28, CD29, CD31, CD43, CD44, CD45RA, CD50, CD54, CD58, CD80, CD102, CD106, and HLA class I, and HLA class II antigen) with various cell lines was compared, mNKES reactivity was found to be unique, not resembling that of any of these mouse mAbs. Interestingly, mNKES specifically and rapidly (within 2 hr) induced homotypic cell aggregation of IM-9 cells. This mNKES-induced cell aggregation was completely blocked by the addition of EDTA and when incubated at 4 degrees C. The mAbs reactive with CD11a/CD18 (leukocyte function-associated antigen-1; LFA-1) and CD54 (intercellular adhesion molecule-1; ICAM-1) completely blocked the IM-9 cell aggregation induced by mNKES, and induction of IM-9 cell aggregation by mNKES was significantly blocked in the presence of the protein kinase C inhibitors sphingosine and H-7 and completely blocked by cytochalasin B and cytochalasin D, which inhibit microfilament formation. Regarding biological function, IM-9 cells bearing surface IgG (sIgG) effectively promoted IgG-secreting activity underlying the homotypic cell aggregation induced by mNKES. The surface antigen recognized by mNKES has a molecular size of about 55 kDa, as determined by immunoblotting analysis. These findings indicate that mNKES recognizes a novel adhesion-associated antigen distinct from any previously reported adhesion-associated antigens in terms of pattern of cellular distribution and biological function and that mNKES is the first human mAb found that rapidly induces homotypic cell aggregation and effectively promotes the IgG-secreting activity of human B lymphoblastoid cell line IM-9.
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PMID:A novel human monoclonal antibody rapidly induces homotypic cell aggregation and promotes antibody-secreting activity by human B lymphoblastoid cell line IM-9. 908 89

The aim of this study was to evaluate the tissue infiltration and phenotypic adhesion profile of 5T2 multiple myeloma (MM) and 5T33 MM cells and to correlate it with that observed in human disease. For each line, 30 mice were intravenously inoculated with myeloma cells and at a clear-cut demonstrable serum paraprotein concentration; mice were sacrificed and a number of organs removed. The haematoxylin-eosin stainings on paraffin sections were complemented with immunohistochemistry using monoclonal antibodies developed against the specific MM idiotype. When analysed over time, 5T2 MM cells could be observed in bone marrow samples from week 9 after transfer of the cells. For the 5T33 MM, a simultaneous infiltration was observed in bone marrow, spleen and liver 2 weeks after inoculation. Osteolytic lesions consistently developed in the 5T2 MM, but this was not consistent for 5T33 MM. PCNA staining showed a higher proliferative index for the 5T33 MM cells. The expression of adhesion molecules was analysed by immunohistochemistry on cytosmears: both 5T2 MM and 5T33 MM cells were LFA-1, CD44, VLA-4 and VLA-5 positive. We conclude that both lines have a phenotypic adhesion profile analogous to that of human MM cells. As the 5T2 MM cells are less aggressive than the 5T33 MM cells, their organ distribution is more restricted to the bone marrow and osteolytic lesions are consistently present, the former cell line induces myeloma development similar to the human disease.
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PMID:Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse. 927 21

7 out of 154 patients with multiple myeloma (MM) with concomitant rheumatoid arthritis (RA) (5 persons) and Bechterev disease (BD) (2 persons) have been presented. There were 5 women and 2 men at age from 52 to 67 years. Four of them had joint's disease for 4, 5, 24 and 25 years prior to MM, and in the next there MM was diagnosed simultaneously with RA. Two patients are still living (50 and 55 months from the diagnosis of MM), the mean survival time of the five already dead was 34.5 months, and did not differ from the survival of patients with MM alone. The contribution of interleukin-6 (Il-6) and adhesion molecules ICAM-1, VCAM-1, CD44 in pathogenesis of both diseases are discussed.
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PMID:[Rheumatoid arthritis as a risk factor for development of multiple myeloma]. 933 71

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