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)

Patients with myeloma have a depressed capacity to respond to antigenic challenge. Studies in this laboratory have previously described an unclassified lymphoid cell which binds human erythrocytes coated with human immunoglobulin G (IgG) anti-D antibody (EA) as important in the inhibition of Ig synthesis in myeloma patients. Using monoclonal antibodies, two-color fluorescence studies, and flow cytometry, we characterized this EA cell as a Leu-1+ (cluster designation (CD) 5), Leu-12+ (CD 19), Leu-16+ (CD 20), B2+ (CD 21), Leu-14+ (CD 22), and HLA-DR+ B cell. The cell was negative for antibodies to Leu-2 (CD 8), Leu-3 (CD 4), Leu-4 (CD 3), Leu-5 (CD 2), Leu-7, Leu-8, Leu-11 (CD 16), Leu-M1 (CD 15), Leu-M3, and CALLA (CD 10). This profile is consistent with a Leu-1+ B cell and excludes a T cell, natural killer cell, and monocyte. Comparison of the relative role of these cells to the role of monocytes in the suppression of pokeweed mitogen-stimulated Ig synthesis was determined in serial studies on 19 myeloma patients. The mean (+/- SEM) percentage of inhibition of Ig synthesis by monocytes from stage I myeloma patients was 14 +/- 2.2%, from stage II patients was 37 +/- 3.5%, and from stage III patients was 51 +/- 4.7%. Inhibition of Ig synthesis by Leu-1+ EA cells was 46 +/- 1.5%, 48 +/- 1.6%, and 43 +/- 3.7% in stage I, II, and III patients, respectively. Immunosuppressive B cells are an important component of inhibition of Ig synthesis in the immunodeficiency of myeloma.
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PMID:Multiple myeloma: an immunologic profile. IV. The EA rosette-forming cell is a Leu-1 positive immunoregulatory B cell. 295 12

The Leu-8 antigen is found on the surface of many hematologic cells, including many T- and B-lymphocytes. With the use of a frozen-section immunoperoxidase technic, 152 B-cell non-Hodgkin's lymphomas were examined for Leu-8 expression. Of these lymphomas, 53% expressed Leu-8. Subclassification of the lymphomas with the use of the International Working Formulation showed that most small lymphocytic, intermediate lymphocytic, and diffuse large cell lymphomas and about half of diffuse small cleaved, diffuse mixed, and follicular lymphomas expressed Leu-8. In contrast, all 17 cases of small noncleaved cell (Burkitt's) lymphoma and 9 of 10 cases of multiple myeloma/plasmacytoma were Leu-8 negative. These results indicate that Leu-8 is expressed on a wide variety of B-cell lymphomas and that differences in Leu-8 expression may be useful in the diagnostic separation of small lymphocytic lymphoma with plasmacytoid features from multiple myeloma/plasmacytoma, and diffuse large cell lymphoma from Burkitt's lymphoma.
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PMID:Expression of the Leu-8 antigen by B-cell lymphomas. 331 Jun 10

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

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

Recurrent bacterial infections due to humoral immunodeficiency are an important cause of death in myeloma patients. Recent data indicate that CD8+ T lymphocytes and a reduction of T helper type 1 cells with disease progression may be involved in the regulation of polyclonal immunoglobulin secretion. In mixed lymphocyte cultures derived from peripheral blood mononuclear cells (PBMC) of 24 myeloma patients with reduced immunoglobulin serum levels we investigated the association of CD4+ and CD8+ T cell subsets and immunoglobulin-secreting B cells (ISC) upon mitogenic stimulation with pokeweed mitogen (PWM) and concanavalin A (Con A). In supernatants of cultured PBMC of myeloma patients the spontaneous secretion of the type 1 cytokine interferon-gamma was reduced. After PWM stimulation reduced numbers of polyclonal ISC were found in 79% of patients, and monoclonal ISC were observed in 12% of patients. After Con A stimulation, again formation of polyclonal ISC was reduced, but monoclonal ISC were found in 41% of patients. Elevation of monoclonal and reduction of polyclonal ISC after stimulation with Con A were associated with an increase of CD8+ CD11b+ Leu-8- T cells (P<0.05). We conclude that the elevated numbers of CD8+ CD11b+ Leu-8- T cells play a role in the stimulation of monoclonal and suppression of polyclonal immunoglobulin secretion in myeloma patients.
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PMID:Elevation of CD8+ CD11b+ Leu-8- T cells is associated with the humoral immunodeficiency in myeloma patients. 927 27

Flow cytometry immunophenotyping of peripheral blood lymphocyte subsets and multivariate data-analytical techniques revealed that among untreated hemato-oncological patients (n = 48) with lymphomas, acute and chronic myeloid and lymphocytic leukemias, monoclonal gammopathy of undetermined significance, and multiple myeloma, 42% had (nonmalignant) lymphocyte profiles clearly distinct from healthy donors. Notably, a similar pattern of increased CD3+ CD57+, CD3+ HLA-DR+, CD3+ CD(16 + 56)+, CD4- CD8+, CD8+ CD57+, CD8+ CD28-, and CD8+ CD62L- subsets was detected. More extensive three-color immunophenotyping on an additional group of 49 untreated patients revealed that both CD4+ and CD8+ T cells displayed significant increases of activation markers: CD69, CD(16 + 56), HLA-DR, CD71, and CD57, and a loss of CD62L and CD28, which is also interpreted as a sign of activation. Consistent with the phenotypical signs of in vivo immune activation, polyclonal cytolytic activity, measured ex vivo in an anti-CD3-redirected assay, was detected within immunomagnetically purified CD4+ T cells of three out of six B-CLL patients investigated, but not within purified CD4+ T cells of five healthy donors. The purified CD8+ T cells of patients (n = 28) and donors (n = 5) on the other hand displayed similar polyclonal cytotoxic activities at the various effector:target ratios investigated. Tumor-directed cytotoxic activity of purified CD4+ (n = 6) and/or CD8+ T cells (n = 15) against freshly isolated autologous tumor cells was not detected in any of the experiments. Collectively, our results demonstrate systemic T cell activation as a common feature in hematological neoplasia, and a markedly enhanced cytolytic activity of the CD4- subset in CLL patients. The reason(s) for this expansion of activated T cells and its pathophysiologic significance, however, remain unclear.
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PMID:Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment. 959 74

The distribution of 27 T-, B-, and natural killer-cell subsets in the peripheral blood of 40 patients with multiple myeloma (MM), ten patients with monoclonal gammopathy of undetermined significance (MGUS), and 40 healthy donors was investigated by means of classical univariate statistics and advanced multivariate data-analytical techniques. The latter approach was used to describe, represent, and analyze lymphocyte subset distribution in a two-dimensional correlation biplot, allowing comparison of complex lymphocyte profiles (i.e., compound lymphocyte subset distributions) of individual subjects rather than isolated subset values of selected patient and/or donor groups. The correlation biplot revealed that, in accordance with the univariate statistics, the MM patients were characterized by marked shifts towards CD8+, CD57+, CD62L-, CD(16+56)+, and HLA-DR+ T cells, suggesting in vivo immune activation. The activation profile was most markedly observed in treated MM patients in the advanced disease stage category. The lymphocyte profiles of MGUS patients were heterogeneous, with approximately half of them located in the swarm of MM patients and the other half in the swarm of healthy donors. Although the univariate statistics revealed significant differences between MGUS patients and healthy donors only within the B-cell compartment, the correlation biplot revealed that two MGUS patients clearly had a typical T-cell activation profile similar to that of the MM patients. One MGUS patient with a T-cell activation profile progressed 13 months later to a stage IA MM and required chemotherapy. A marked lymphocyte profile shift in one MM patient was associated with terminal and aggressive disease transformation. Our study illustrates further the practical use of correlation biplots for the detection of aberrant lymphocyte profiles and/or profile shifts in individual patients.
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PMID:Lymphocyte profiles in multiple myeloma and monoclonal gammopathy of undetermined significance: flow-cytometric characterization and analysis in a two-dimensional correlation biplot. 969 12

The efficacy of an immunomagnetic purging method and the Isolex 300 devices were assessed for selecting CD34+ cells from leukapheresis products of 29 patients with non-Hodgkin's lymphoma (NHL), 39 with multiple myeloma and 34 with breast cancer. The mean purity of the CD34+ cell population was 93.6% and the mean recovery was 67.7%. Following enzymatic cleavage by chymopapain the expression of Thy-1 and Leu-8 was significantly reduced without affecting haematological recovery. The population of selected CD34+ cells of 4/8 patients with follicular lymphoma became PCR-negative. A 2.5 log reduction of tumour cells could be achieved in four patients with multiple myeloma as shown by a quantitative PCR assay. There were no tumour cells detectable in any of the 19 CD34+ cell preparations of patients with breast cancer. In 64 patients who received 94 cycles of high-dose therapy, a mean number of 4.7x 10(6) CD34+ cells/kg were autografted. The time needed for platelet reconstitution was different when a comparison was made with 156 patients, who had received unmanipulated leukapheresis products (10 v 12 d, P = 0.006). No significant differences with regard to neutrophil recovery were noted. Five patients had a graft failure. Two of them died (on day 78 and 88 following PBSCT), and three patients were rescued with unmanipulated back-up transplants. In conclusion, the immunomagnetic selection of CD34+ cells provides autografts with reduced tumour cell content and an engraftment ability similar to that of unmanipulated autografts.
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PMID:Autografting with CD34+ peripheral blood stem cells: retained engraftment capability and reduced tumour cell content. 1005 Jul 23

Human bone marrow stroma (BST)-dependent myeloma sister cell lines MOLP-6 and MOLP-7 were established from the peripheral blood of a multiple myeloma (MM) patient with IgA kappa type MM (stage IIIB). The growth of the cell lines is constitutively dependent on BST cells; none of the cytokines tested nor the culture supernatant of the BST cells could support the growth. Both cell lines showed typical plasma cell morphology with abundant cytoplasm and one to four nuclei under Wright staining. The immunoprofiles of MOLP-6 and MOLP-7 correspond to that seen typically in primary MM cells: positive for cytoplasmic immunoglobulin (Ig) chains, a heavy and kappa light chains, CD9, CD28, CD40, CD44, CD45, CD56, and PCA-1; the cells were negative for surface Igs and various other B-cell, T-cell and myelomonocyte associated markers. Both cell lines also expressed adhesion molecules including HCAM (CD44), VLA-4 (CD49d/CD29), VLA-6 (CD49f/CD29), ICAM-1 (CD54), NCAM (CD56), LFA-3 (CD58) and L-selectin (CD62L). The doubling time of MOLP-6 and MOLP-7 was 48 and 168 hours, respectively. In addition to this growth characteristic, the maximum cell density of each cell line was obtained at 1.7 x 10(6) cells/ml and 9.7 x 10(5) cells/ml, respectively. The characteristics of each cell line may reflect intraclonal variation of the proliferative capacity. The MOLP-6 together with the MOLP-7 sister will be useful model systems for the investigation of the biology of myeloma.
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PMID:Human bone marrow stroma-dependent myeloma sister cell lines MOLP-6 and MOLP-7 derived from a patient with multiple myeloma. 1093 46

To investigate whether superantigen (SAG) from endogenous mouse mammary tumor virus functions as an immunogenic or a tumorigenic factor in tumor development, the BALB/c myeloma cell line FO was transfected with the SAG gene from the 3' Mtv-50 long terminal repeat (LTR) open reading frame (ORF), the product of which was specific for Vbeta6. All five transfectants expressing Mtv-50 LTR ORF mRNA showed stimulatory activity for Vbeta6 T-cell hybridomas in vitro; this activity was inhibited by the addition of anti-Mtv-7 monoclonal antibody (MAb) or anti-major histocompatibility complex class II I-A(d) and I-E(d) MAb. All transfectants with the SAG gene grew more rapidly than did mock transfectants in BALB/c mice after subcutaneous inoculation, whereas all clones, including mock transfectants, grew equally well in athymic nude mice. A significant fraction of Vbeta6 T cells selectively expressed activation markers, including CD44(high), CD62L(low), and CD69(high), and produced large amounts of interleukin 5 (IL-5) and IL-6 in BALB/c mice inoculated with transfectants. These results suggested that the expression of viral SAG enhances the tumorigenicity of a myeloma cell line through the stimulation of SAG-reactive T cells.
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PMID:Expression of mouse mammary tumor virus superantigen accelerates tumorigenicity of myeloma cells. 1095 19


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