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)

Bone marrow samples from 55 patients with multiple myeloma (MM) and 23 patients with monoclonal gammopathy of undertermined significance (MGUS) were evaluated with a broad panel of monoclonal antibodies. Plasma cells from 78% (43/55) of patients with MM strongly expressed the natural killer cell antigen CD56 (NKH-1, Leu-19). Of the 23 patients with MGUS, none showed strong CD56 reactivity, although three had weak reactivity in less than 20% of plasma cells. Myeloma cells expressing CD56 did not coexpress the CD57 or CD16 antigens. Patients with CD56-positive plasma cells had both indolent and aggressive disease. However, the 12 CD56-negative patients had predominantly aggressive disease with an unexpected preponderance of kappa Bence Jones only myeloma (5/10[50%] evaluable patients). Polyclonal plasma cells from non-neoplastic tissue sites (normal bone marrows, lymph nodes, tonsillar biopsies, and gut-mucosa biopsies) showed a near absence of CD56. We conclude that isolated, strong CD56 expression is common in MM, but not in MGUS or reactive plasma cells. The potential biologic importance of CD56 positivity in myeloma is reviewed.
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PMID:Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). 169 13

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.
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PMID:Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells. 172 26

We investigated the expression of CD56 (a neural cell adhesion molecule, NCAM) and CD57 in various hematopoietic and non-hematopoietic malignant cells, using Leu-19 and Leu-7 monoclonal antibodies. Although both molecules are commonly defined as a natural killer cell marker, we found that CD56 was highly expressed on blasts from patients with acute monocytic (4/6) and megakaryocytic (3/3) leukemias. In the latter, FACS two-color analysis revealed that leukemic megakaryoblasts simultaneously expressed CD56 and platelet-related antigens. Among leukemic cell lines, one myelocytic, three monocytic, and two megakaryocytic lines were positive for CD56. On the other hand, except for one large granular lymphocytic leukemia and one multiple myeloma cell line, none of the lymphoid leukemia cell lines or lymphoblasts from patients with acute lymphocytic leukemia (ALL) (0/15), non-Hodgkin's lymphoma (NHL) (0/2), and central nervous system (CNS) leukemia (0/2) reacted with Leu-19 antibody for CD56. The expression of CD56 in leukemia cells was not significantly affected by 12-O-tetradecanoylphorbol-13-acetate (TPA). By contrast, all hematopoietic materials were negative for CD57, while non-hematopoietic neuroblastoma cell lines expressed this molecule (4/5) as well as CD56 (5/5). Cytogenetically, the NCAM gene is located at chromosome 11q23, and chromosome breaks were often observed at this location in various leukemias. Blasts from all five acute non-lymphocytic leukemia (ANLL) patients and cell lines with 11q23-proximal chromosomal breaks were positive, while those from one ALL patient with an 11q23 abnormality were negative for CD56, necessitating further studies to clarify the link between the 11q23 abnormality and CD56 expression.
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PMID:Expression of CD56/NCAM on hematopoietic malignant cells. A useful marker for acute monocytic and megakaryocytic leukemias. 172 53

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

We studied the effect of classical (Pavlovian) conditioning of the natural killer cell response on survival of tumor-bearing mice. Mice were given repeated injections of poly I:C every three days paired with exposure to the odor of camphor for 4 hours. First, we investigated the possible therapeutic effect of repeated exposure to the odor of camphor on the growth of MOPC 104E murine myeloma. The results indicate that camphor alone had no therapeutic effect when the mice were exposed to the odor of camphor after tumor transplantation. We then investigated the effect of repeated exposure to camphor prior to tumor transplantation and subsequent repeated exposure to camphor following tumor transplantation. Again, we observed no therapeutic benefit. In a third experiment, we examined the effect of the conditioned poly I:C response on the growth of the murine myeloma. Animals in the conditioned group had an increase in median survival (day 43, as compared to days 34, 38, 37 of various control groups). Two of these conditioned mice lived more than 120 days and showed early tumor growth, but were free of disease at day 97. During the course of the study conditioned mice received no additional treatment other than being reexposed to camphor every third day.
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PMID:Influence of conditioned natural immunity on tumor growth. 347 95

Monoclonal gammopathy of undetermined significance (MGUS) is different from multiple myeloma (MM) by a low proliferation and by its indolent clinical course. In this study, two biological parameters were investigated which mark the transition from MGUS to MM, i.e. expression of the P-170 glycoprotein associated with the multidrug resistance phenotype (MDR-1) and expression of the natural killer cell antigen. CD56. Strong MDR-1 expression was found in plasma cells of 32/38 untreated MGUS as compared with 33/105 untreated MM stage I-III (84% v 32%, P < 0.001) and in 0/10 normal plasma cell samples. CD56 expression in high density was present in 43/57 analysed untreated MM but in none of 23 MGUS (78% v 0%, P < 0.0001). Plasma cells did characteristically show a low Ki-67 proliferation index in 14/15 MGUS patients (mean 0.05%, range 0-0.2%) and a higher index in 25 analysed MM patients (mean 2.31%, range 1-7%, P < 0.03). These data indicate that MDR-1 expression together with absence of CD56 expression and a low proliferation index can be used to separate MGUS from MM.
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PMID:Analysis of multidrug-resistance (MDR-1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma. 767 88

The risk of cancer was evaluated among 77,952 asthma patients with bronchial asthma. The series was obtained through linkage of two registers: the Finnish Social Insurance Institution's file of asthma patients and the Finnish Cancer Registry. There was a significant excess risk of lung cancer in both sexes, the standardized incidence ratio (SIR) being 1.32 among men and 1.66 among women. In women, the risk of cancer of the rectum was significantly increased (SIR 1.42), whereas the risks of cancer of the corpus uteri and multiple myeloma were lower than expected (SIR 0.76 and 0.53, respectively). In men, the incidence of cancer of the larynx was significantly reduced (SIR 0.63) and that of the bladder increased (SIR 1.25). When both sexes were combined, cancers of the colon (SIR 1.17) and rectum (SIR 1.28) also showed a significantly elevated risk. A reduction in risk was seen in stomach cancer (SIR 0.88) and lymphatic leukaemia (SIR 0.55). The increased lung cancer risk may be due to local inflammatory changes. It is possible that differences in the immune system, e.g. natural killer cell activity, explain some of the reduced cancer risks.
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PMID:Cancer incidence among 78,000 asthmatic patients. 814 10

Characterisation of murine hybridoma cell lines derived from the fusion of lymphocytes migrating from explant cultures of early, pregnancy-associated metrial glands (days 6-8 of gestation) to SP 2/0 cells, has been extended (van den Heuvel et al., J. Reprod. Immunol., 27 (1994) 13-36). These hybridomas have been grown in culture for over 2 years and are thought to represent the only immortalized lines of murine pregnancy-associated, uterine natural killer (uNK) cells. Previous studies had shown that these hybridomas, known as GWM cells, lack uNK cell surface markers, but share with uNK cells the expression of the lytic protein perforin and the ability to lyse YAC cells, a natural killer cell target (van den Heuvel et al., J. Reprod. Immunol., 27 (1994) 13-36). We report here, the evaluation of the transcription and expression of genes encoding the estrogen receptor (ER), the progesterone receptor (PR) and the interleukin 2 receptor complex (IL 2R alpha, beta and gamma) by uNK cells at day 8 of gestation and by GWM 1-2 cells and SP 2/0 cells. Our investigations indicate that expression of these genes divides day 8 uNK cells into subsets, with the predominant population being ER+, PR-, IL 2R alpha +, IL 2R beta + and IL 2R gamma +. Like day 8 uNK cells, most GWM 1-2 cells expressed all three chains of the IL 2R complex. In addition, GWM 1-2 cells expressed the ER but the PR was not detected on this cell line. Only the IL 2R alpha was detected on the SP 2/0 myeloma cell line. These studies further validate the use of GWM hybridomas as models for pregnancy-associated uNK cells.
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PMID:An analysis of the uterine lymphocyte-derived hybridoma cell line GWM 1-2 for expression of receptors for estrogen, progesterone and interleukin 2. 888 21

Natural killer cell activity and related cell surface markers of peripheral blood lymphocytes were studied in 73 patients with multiple myeloma, 25 with monoclonal gammopathy of undetermined significance and 20 normal controls. Natural killer cell number was significantly higher in both multiple myeloma and monoclonal gammopathy patients than in controls, whereas the natural killer activity of multiple myeloma patients was inversely related to their disease status. Incubation of peripheral blood lymphocytes or natural killer cells with IgG myeloma proteins purified from several patients induced a down-modulation of basic natural killer activity. This inhibitory effect of monoclonal IgG was dose dependent and significantly stronger in patients with active (at diagnosis and at relapse) than stable multiple myeloma or in normal controls. Addition of exogenous recombinant interleukin-2 restored natural killer cell activity against K562 target cells, indicating that natural killer cells were able to recover their functions. However, recombinant interleukin-2-stimulated natural killer cells were responsive to down-modulation of monoclonal IgG. These data suggest that impaired natural killer cell function in active multiple myeloma is caused by the inhibitory effect of M-component.
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PMID:IgG M-components in active myeloma patients induce a down-regulation of natural killer cell activity. 914 27

Plasmapheresis (PP), staphylococcal protein A immunoadsorption (SPI), and extracorporeal photochemotherapy (EP) have been utilized in cancer treatment for about 20 years. PP removes immune complexes and induces a temporary increase in T4/T8 ratio, natural killer cell activity, and blastogenic responses. SPI removes immune complexes, enhances lymphocytic responses, and activates complement. EP increases lysis of circulating lymphoma cells by CD8+ cytotoxic T cells and increases tumor necrosis factor production by host monocytes. PP induces partial remission in about 28% of patients, but this remission is short lived. SPI gives similar results. Addition of PP to chemotherapy has been reported to prolong survival in patients with multiple myeloma. EP appears useful in treating cutaneous T cell lymphomas with 25% of patients achieving complete response and 50% of patients attaining partial remission. Thus, PP and SPI induce short-lived immune responses, but have no proven clinical utility. EP may be useful in the treatment of cutaneous T cell lymphomas.
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PMID:Therapeutic apheresis in malignancy. 1022 77


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