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

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.
 ...
PMID:[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth]. 786 16

Human peripheral blood eosinophils adhered specifically to microtitre plates coated with plasma fibronectin (Fn) in a dose- and time-dependent fashion. Adhesion was optimal at 60 min at a concentration of 100 micrograms/ml. Adherence to Fn was up-regulated by platelet-activating factor (PAF; optimum concentration of 10(-6) M) and was significantly inhibited by a polyclonal anti-Fn antibody (P < 0.05). The following evidence suggested that eosinophil adhesion to Fn was mediated by alpha 4 beta 1: (1) eosinophil adherence to Fn was not inhibited by an Arg-Gly-Asp-Ser (RGDS) synthetic peptide; (2) there was a dose-dependent adherence of eosinophils to microtitre plates coated with the 40,000 MW proteolytic fragment of Fn that contains the CS-1 alpha 4 beta 1 binding region, whereas adherence to the 120,000 MW chymotryptic fragment of Fn, which contains the RGD-dependent binding site, was weak and only observed at high concentrations (> 250 micrograms/ml); (3) significant inhibition of eosinophil adherence to Fn was achieved by monoclonal antibodies (mAb) against the alpha chain of VLA-4 but not by a mAb against CD45 or a mouse myeloma antibody as negative controls. After adhesion to Fn, eosinophils were investigated for their capacity to release leukotriene C4 in response to stimulation with a suboptimal concentration of calcium ionophore (2 x 10(-6) M). Significant enhancement of release was detected with Fn-coated plates but not with the control bovine serum albumin (BSA) (P < 0.01). Furthermore, this enhancement was significantly inhibited by the alpha 4 beta 1 mAb HP2/1 (P < 0.05) but not by an anti-CD45 mAb. From these studies we conclude that (1) alpha 4 beta 1 (VLA-4) integrin is a major receptor for Fn on human eosinophils and (2) adhesion to Fn may prime eosinophils for mediator release during allergic inflammation.
 ...
PMID:Adhesion to fibronectin primes eosinophils via alpha 4 beta 1 (VLA-4). 792 93

A myeloma cell line (KHM-11) was established from the pleural effusion of a patient with IgA-kappa type aggressive myeloma with high serum lactate dehydrogenase who was extremely resistant to vincristin, adriamycin and dexamethasone combination therapy (VAD). The morphology of fresh tumor cells and KHM-11 was plasmablast according to Greipp's criteria. In addition to the expression of regular plasma cell antigens, CD38 and PCA-1, CD45 was found on both fresh cells and KHM-11. Other T- or B-cells antigens, such as CD2, 4, 8, 19, and 20 were negative. Cytoplasmic immunoglobulin kappa light chain in KHM-11 was found by flowcytometry. Southern blot analysis revealed that fresh sample and KHM-11 shared the same immunoglobulin gene rearrangement. IL-6 was found in the culture supernatant of KHM-11, and this supernatant stimulated the growth of this cell line, indicating an IL-6 autocrine mechanism. These findings indicate that KHM-11 is a CD45-positive immature plasma cell line. As far as we know, there is no report of CD45-positive myeloma cell line. KHM-11 should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.
 ...
PMID:Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase. 793 74

The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.
 ...
PMID:Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen. 842 68

Interleukin-6 (IL-6) has been suggested to play a major role in multiple myeloma. To investigate the source and target cells of IL-6 activity in multiple myeloma, expression of the cytokine and its receptor genes by myeloma plasma cells was studied. Tumor cells were sorted from bone marrow aspirates of myeloma patients using 4-parameter gating. Myeloma cells were identified as CD38high CD45negative-intermediate and by their light-scatter characteristics. Sorted cells contained only myeloma plasma cells. No contaminating cells were present as determined morphologically, by monoclonal cytoplasmic Ig analysis, and by polymerase chain reaction (PCR) amplification of marker genes. Myeloma cells from 45% of patients expressed IL-6. IL-6 receptor transcripts were found in 68% of the specimens. IL-6 gene expression correlated with expression of the IL-6 receptor gene (P < .005). Correlations observed between the expression of CD45, a protein tyrosine phosphatase expressed by B lymphocytes but not by plasma cells, and the expression of the IL-6 and IL-6-receptor genes (P < .0002 and P < .005, respectively) suggest that an autocrine IL-6 loop is functioning in myeloma in preplasma cells.
 ...
PMID:Interleukin-6 gene expression in multiple myeloma: a characteristic of immature tumor cells. 850 73

Overexpression of the transmembrane protein-tyrosine phosphatase (PTPase) CD45 in nonhematopoietic cells results in decreased signaling through growth factor receptor tyrosine kinases. Consistent with these data, insulin receptor signaling is increased when the CD45-related PTPase LAR is reduced by antisense suppression in a rat hepatoma cell line. To test whether the hematopoietic cell-specific PTPase CD45 functions in a manner similar to LAR by negatively modulating insulin receptor signaling in hematopoietic cells, the insulin-responsive human multiple myeloma cell line U266 was isolated into two subpopulations that differed in CD45 expression. In CD45 nonexpressing (CD45-) cells, insulin receptor autophosphorylation was increased by 3-fold after insulin treatment when compared to CD45 expressing (CD45+) cells. This increase in receptor autophosphorylation was associated with similar increases in insulin-dependent tyrosine kinase activation. These receptor level effects were paralleled by postreceptor responses. Insulin-dependent tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and Shc was 3-fold greater in CD45- cells. In addition, insulin-dependent IRS-1/phosphatidylinositol 3-kinase association and MAP kinase activation in CD45- cells were also 3-fold larger. While expression of CD45 was associated with a decrease in the responsiveness of early insulin receptor signaling, interleukin 6-dependent activation of mitogen-activated protein kinase kinase and mitogen-activated protein kinase was equivalent between CD45- and CD45+ cells. These observations indicate that CD45 can function as a negative modulator of growth factor receptor tyrosine kinases in addition to its well-established role as an activator of src family tyrosine kinases.
 ...
PMID:The transmembrane protein-tyrosine phosphatase CD45 is associated with decreased insulin receptor signaling. 855 83

The blood of most patients with active multiple myeloma (MM) contains cells related to the bone marrow tumor. However, identifying clonal cells in the blood of patients with monoclonal gammopathy of undetermined significance (MGUS) has been difficult. In this study, we analyzed blood mononuclear cells (BMNCs) from 16 patients with MGUS, 2 with amyloidosis, 8 with smoldering MM (SMM), 2 with indolent MM (IMM), and 15 with active MM using three different methods to detect and quantitate clonal cells, ie, immunofluorescence microscopy (IM) for monoclonal plasma cells, three-color flow cytometry (FC) for CD38(+)CD45- CD45(dim) cells, and the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). Using ASO-PCR, we were able to detect clonal cells in the blood in 13 of 16 patients with MGUS, 2 of 2 with amyloid, 6 of 8 with SMM, 2 of 2 with IMM, and 13 of 15 with MM. In 9 of the 13 patients with MGUS with blood involvement, the number of clonal cells was very small ( < 0.04% of the BMNCs). The median percentage of clonal cells as determined by ASO-PCR was 0.02 for MGUS, 0.02 for SMM, and 0.24 for MM. Clonal plasma cells or CD38+CD45-CD45(dim) cells were identified by IM or FC in 6 of 16 MGUS patients, 4 of 8 with SMM, and 11 of 15 with MM. In all cases in which IM or FC detected clonal cells, the ASO-PCR was positive. This study shows that, by using ASO-PCR, clonal cells can be found at very low levels in the blood in most patients with MGUS. However, the number of clonal cells in the blood of MGUS patients is less than those with overt MM (P = .006). In contrast to MGUS, patients with active MM are more likely to have identifiable clonal circulating plasma cells (P = .05).
 ...
PMID:Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. 870 85

For patients with multiple myeloma the most important laboratory correlate of prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell labelling index (LI). However, the traditional immunofluorescent microscope LI technique, like other manual enumeration assays, can suffer from poor precision and accuracy. In this study the LI of different subpopulations of plasma cells (CD38++) as determined by flow cytometry was correlated with disease state. The mean LI of the total CD38++ population was significantly higher (2.7 +/- 0.4%) than the LI determined by the traditional slide technique (0.6 +/- 0.1%) for 65 samples tested. Primitive plasma cells (CD38++, CD45++) had a higher labelling index than mature plasma cells (CD38++, CD45-) (7.0 +/- 1.3% v 1.8% +/- 0.3%) and in one patient the LI of the primitive plasma cells was 46%. In addition, the LI of the mature plasma cells was lower than the total plasma cell population. As expected, there was a significant difference between the LI of patients in plateau phase and progressive disease but this difference was greatest when the LI of the primitive plasma cells was studied (9.2 +/- 2.9% v 2.2 +/- 0.7%; z = 19.9, P < 0.001). This study has raised some concerns about the sensitivity and accuracy of the traditional labelling index and has shown that the increased LI associated with progressive disease is almost entirely attributable to an increase in the LI of the primitive plasma cell subpopulation and that the LI of primitive plasma cells provides a more clinically significant correlation with disease status than the traditional assay.
 ...
PMID:The labelling index of primitive plasma cells determines the clinical behaviour of patients with myelomatosis. 1191 67

Bone marrow plasma cells (PC) from patients with multiple myeloma (MM) express monoclonal cytoplasmic immunoglobulin (clg) light chain, strongly express CD38, and usually lack or dimly express CD45. The detection of malignant plasma cells in the peripheral blood (PB) by immunofluorescence microscopy (IM) distinguishes patients with active MM from those with stable disease. The aim of this study was to learn whether two-color (CD38 and CD45) flow cytometry (FC) on whole blood specimens (WBFC) and three-color FC (CD38, CD45, and anti-kappa or lambda clg) on mononuclear cells could identify circulating PC as well as the standard, more labor intensive IM technique. Split-samples of PB from 73 patients with plasma cell proliferative disorders were examined by both techniques. WBFC detected CD38+ CD45- cells in 94% (33/35) of patients with circulating monoclonal PC detected by IM and three-color FC detected monoclonal CD38+ CD45- cells in 77% (27/35) of these cases. The absolute number of monoclonal PC detected by IM was compared to the FC methods and the Spearman rank correlations were 0.77 with WBFC and 0.80 with three-color FC. This study indicates that WBFC, using antibodies to CD38 and CD45, offers a practical and reliable method to detect and quantify circulating malignant PC in patients with MM.
 ...
PMID:Detection of myeloma cells in the peripheral blood by flow cytometry. 881 86

Monoclonal plasma cells (CD38+CD45-/dim) are typically present in the blood of patients with active myeloma and can contaminate stem cell harvests. This has led to strategies that select CD34+ cells for use in autologous stem cell transplantation with the goal of decreasing tumor cell contamination. The aim of this study was to learn if the CD34 antigen is expressed on monoclonal plasma cells in the blood or marrow of patients with multiple myeloma. We used three-color flow cytometry (surface CD38;CD45 and cytoplasmic kappa or lambda) to identify monoclonal plasma cells in the blood (n = 24) and marrow (n = 37) from patients with plasma cell proliferative disorders. In each case the CD38+CD45- and CD38+CD45dim+ monoclonal populations were then analyzed for CD34 expression. In all 24 blood and 37 marrow samples, the CD38+CD45-monoclonal plasma cells were negative for CD34 expression. CD38+CD45dim+ monoclonal cells were documented in the blood of 11 patients and in the marrow of 33 patients and this cell population was also CD34-negative in all cases. These results indicate that CD34 is usually not expressed on the CD38+CD45-CD45dim+ monoclonal plasma cells in the blood or marrow of patients with plasma cell proliferative disorders. CD34 selection methods should therefore decrease the chance of tumor cell contamination of the stem cell product.
 ...
PMID:Expression of the hematopoietic stem cell antigen CD34 on blood and bone marrow monoclonal plasma cells from patients with multiple myeloma. 908 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>