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

The growth of myeloma cells is believed to be mediated by functional interactions between tumor cells and the marrow environment involving the action of several cytokines. We report on the establishment and characterization of a new human myeloma cell line (TAB1) that can be long-term maintained in the presence of conditioned medium of bone marrow stromal cells (BMCM) and a BMCM independent variant, C2-2. Both cell lines have plasma cell morphology and express plasma cell antigens (CD38, PCA-1 and immunoglobulin kappa light chain). In the absence of BMCM, TAB1 cells undergoing apoptosis were observed. Among the adherent molecules tested, these cells expressed VLA-4, ICAM-1 and H-CAM, but not VLA-5, suggesting that these were mostly immature plasmacytes. Introduction with exogenous IL-6 and/or GM-CSF, which were detected in BMCM, partially supported the proliferation of TAB1 cells. Treatment with anti-IL-6 antibody partially inhibited the proliferation of TAB1 cells cultured with BMCM. These findings strongly suggest that TAB1 required at least two or more factors on their growth in vitro; IL-6 was one of the factors necessary for cell growth. Further studies are required to clarify the precise molecules which support TAB1 cell growth in combination with IL-6, however, TAB1 and its variant C2-2 cells may offer an attractive model to unravel novel molecular mechanisms involved in bone marrow stroma-dependent growth of myeloma cells.
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PMID:Requirement of soluble factors produced by bone marrow stromal cells on the growth of novel established human myeloma cell line. 1257 18

A case of primary plasma cell leukemia with hairy-cell morphology and lambda-type Bence-Jones protein is reported. Most of the atypical cells in the peripheral blood of this case were small lymphoid cells or lymphoplasmacytoid lymphocytes with numerous cytoplasmic hairy projections. Plasmablastic cells and 'tadpole'-like cells were also present in the bone marrow. Immunohistochemically, these atypical cells expressed the cytoplasmic lambda light chain and surface CD38 proteins but were negative for B-cell markers such as CD19, CD20 and CD79a. VLA-5 (CD49e), which is supposed to be expressed in mature populations of plasma cells, was negative. A sequence analysis of the variable region gene in the light-chain (V(L)) and heavy-chain (V(H)) loci of immunoglobulin demonstrated significant somatic hypermutation and intraclonal nucleic acid sequence variations. To our knowledge, the intraclonal diversity of these loci has been previously reported in some cases of monoclonal gammopathy of undetermined significance (MGUS), but never in a case of multiple myeloma. The immunohistochemical and molecular characteristics of this case allowed us to delineate the origin of the leukemic cells with hairy cell-morphology as germinal center B-cells, which would be at a more immature stage than the presumable origin of multiple myeloma.
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PMID:A case of primary plasma cell leukemia with hairy-cell morphology and lambda-type Bence-Jones protein. Immunohistochemical and molecular analysis. 1286 67

Cytokines exert multiple biological functions through binding to their specific receptors that triggers activation of intracellular signaling cascades. The cytokine-mediated signals may produce variable and even opposing effects on different cell types, depending on cellular context, which also are dictated by the differentiation stage of the cell. Multiple myeloma is a monoclonal proliferative disorder of human plasma cells. Despite their clonal origin, myeloma cells appear to include mixed subpopulations in accordance with expression of their surface antigens, such as CD45, CD49e, and MPC-1. Although interleukin-6 (IL-6) is widely accepted as the most relevant growth factor for myeloma cells in vitro and in vivo, only a few subpopulations of tumor cells, such as CD45(+)MPC-1(-)CD49e- immature cells, proliferate in response to IL-6. We recently showed that IL-6 efficiently activated both signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) in CD45- myeloma cell lines, although CD45- cells failed to proliferate in response to IL-6. In contrast, src family protein-tyrosine kinases (PTKs), the most important substrates for CD45 protein-tyrosine phosphatase (PTP) are found activated independently of STAT3 and ERK1/2 activation in CD45+ but not in CD45- myeloma cell lines. Therefore activation of both STAT3 and ERK1/2 is not sufficient for IL-6-induced proliferation of myeloma cells, which requires the src family kinase activation associated with CD45 expression. We propose a mechanism for IL-6-induced cell proliferation that is strictly dependent on the cellular context in myelomas.
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PMID:Interleukin-6-induced proliferation of human myeloma cells associated with CD45 molecules. 1295 2

Multiple myeloma (MM) is a proliferative disorder of monoclonal plasma cells which accumulate in human bone marrow, and myeloma cells proliferate in response to a cytokine, interleukin-6 (IL-6). We recently found that MPC-1- CD49e- immature myeloma cells expressing CD45 form a proliferating population in MM. IL-6 activates at least two intracellular pathways including signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) following the activation of Janus kinases (JAKs) via its receptor complexes composed of the IL-6 receptor alpha chain and gp130. Although the roles of CD45 have been extensively studied for antigen receptors in B and T cells, its physiological consequences in other hematopoietic cells remain largely unknown. Myeloma cells expressing CD45 antigens which contain the activation of src family protein-tyrosine kinases (PTKs) independent of IL-6 stimulation proliferate in response to IL-6, whereas the proliferation of CD45- cells which lack a considerable activity of the src family PTKs is not promoted by IL-6. The STAT3 and ERK1/2 pathways are similarly activated by IL-6 in both cells either expressing or not expressing CD45. In this review, we argue a novel mechanism of proliferation of myeloma cells, in that the activation of both STAT3 and ERK1/2 is not sufficient for IL-6-induced proliferation which further requires IL-6-independent activation of the src family kinases associated with CD45 phosphatase. We propose that the cellular context, such as CD45 expression and src family kinase activation, is crucial for myeloma cells to proliferate in response to IL-6.
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PMID:Interleukin-6, CD45 and the src-kinases in myeloma cell proliferation. 1456 47

Adhesion molecules and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling play key roles in homing and mobilization of hematopoietic stem cells (HSC). Active signaling through SDF-1/CXCR4 and upregulation of adhesion molecules are required for homing, whereas downregulation of adhesion molecules and disruption of SDF-1/CXCR4 signaling are required for mobilization of HSC. We studied the surface expression of CXCR4 very late activation antigen (VLA)-4 and VLA-5 on myeloma cells mobilized with cyclophosphamide and GM-CSF in 12 multiple myeloma patients undergoing HSC mobilization for autologous transplantation. We also studied the plasma levels of SDF-1 in apheresis collection of these patients. We observed a statistically significant decrease in the levels of SDF-1 and surface expression of CXCR4 on myeloma cells in four consecutive apheresis collections compared with premobilization bone marrow specimens. We also observed a statistically significant decrease in surface expression of VLA-4 in myeloma cells in the apheresis collections compared with premobilization bone marrow samples. Furthermore, myeloma cells derived from apheresis collections had decreased adhesion and trans-stromal migration in response to SDF-1, which could be reversed by short incubation with interleukin-6. Hence, mobilization of myeloma cells involves SDF-1/CXCR4 signaling and downregulation of VLA-4.
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PMID:Mobilization of myeloma cells involves SDF-1/CXCR4 signaling and downregulation of VLA-4. 1468 92

In our experience with thalidomide treatment for refractory multiple myeloma (MM), most patients with progressive disease (PD) did not show an increase in M-protein despite the tumor burden of myeloma cells. This finding led us to suspect that proliferation of immature myeloma cells showing MPC-1(-)/CD49e(-) phenotype may be a sign of PD. We report the results of consecutive analysis of the phenotype of myeloma (plasma) cells in an MM patient with PD during treatment with thalidomide. The myeloma cells decreased by thalidomide therapy were mature (MPC-1(+)/CD49e(+)) and intermediate (MPC-1(+)/CD49e(-)) types. When the patient was in the PD state, extramedullary plasmacytoma was recognized without proliferation of myeloma cells in the bone marrow (BM). The phenotype of myeloma (plasma) cells in both of these locations was that of immature myeloma cells (MPC-1(-)/CD49e(-)), and they showed decreased intensity of CD38 expression. The level of immunoglobulin G (IgG) in serum was decreased, and myeloma (plasma) cells in BM did not increase in PD. Although these clinical features may not be specific to MM patients in PD undergoing treatment with thalidomide, we suggest that immature myeloma cells may be resistant to thalidomide.
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PMID:Progressive myeloma after thalidomide therapy in a patient with immature phenotype of myeloma (plasma) cells. 1521 67

We describe an 89-year-old woman who presented with prominent plasmacytosis mimicking plasma cell leukemia. The apparent serum M-protein level of > 7 g/dL of gamma mobility was revealed to be a polyclonal increase of immunoglobulins. The plasma cells in the peripheral blood expressed polyclonal surface/cytoplasmic immunoglobulins as well as CD19, CD30, CD38, and CD138 antigens but lacked CD10, CD20, CD25, and CD56. The bone marrow plasma cells showed the CD45+, CD19+, CD56-, MPC-1(-/+), and CD49e- immunophenotype, which was in clear contrast with the immunophenotypes of the neoplastic myeloma cells. Abdominal lymphadenopathy, splenomegaly, and a high level of soluble interleukin 2 receptor may have been reflections of an underlying lymphoproliferative disorder, potentially leading to the polyclonal proliferation of plasma cells.
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PMID:Polyclonal proliferation of plasma cells associated with marked hypergammaglobulinemia in an elderly patient. 1571 91

We analyzed both morphologic and phenotypic findings of myeloma cells before and after chemotherapy in 21 patients with multiple myeloma. The morphologic analysis was based on the Greipp classification, and phenotypic analysis was performed by 3-color flow cytometry using the CD38 plasma gating method (Marrow plasma 38). Results with flow cytometry using a combination of MPC1, CD49e, and CD45 supported the morphologic findings for the myeloma cells. Treatment with 3 or 4 cycles of VAD (vincristine, doxorubicin, and dexamethasone) therapy was effective in reducing the total numbers of myeloma cells, but the proportion of immature myeloma cells increased after this treatment. However, the immature myeloma cells were reduced by high-dose melphalan (HD-Mel) therapy followed by autologous stem cell transplantation (ASCT). High-dose cyclophosphamide treatment for stem cell harvesting did not show an effect on the residual immature myeloma cells after VAD treatment. In addition, thalidomide was not effective in reducing the numbers of immature myeloma cells. These results suggest that VAD (3 or 4 cycles) therapy plus HD-Mel followed by ASCT is a reasonable treatment for multiple myeloma and that Marrow plasma 38 analysis is a useful method for monitoring the response of multiple myeloma to chemotherapy.
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PMID:The maturation of myeloma cells correlates with sensitivity to chemotherapeutic agents. 1591 66

Previous studies showed that 2-methoxyestradiol (2ME2) could suppress the proliferation of myeloma cells and induce their apoptosis. In the present study, we found that treatments with low-concentration of 2ME2 resulted in some maturing morphological changes of myeloma cells. Flow cytometric analysis showed that the expression of CD49e on the myeloma cells surface was significantly increased by 2ME2. Moreover, 2ME2 increased the secretion of light chain protein remarkably. Furthermore, the expressions of transcription factor XBP-1 mRNA and protein were also up-regulated. These results demonstrated that 2ME2 at low-concentration could induce differentiation of the myeloma cells, which would provide a new, safe strategy for myeloma therapy.
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PMID:2-Methoxyestradiol at low dose induces differentiation of myeloma cells. 1603 32

The heterogeneity of bone marrow plasmacytosis is clearly analyzed by multicolor staining with anti-CD38 antibody. To date, at least 5 subpopulations of plasma cells have been identified in the bone marrow of multiple myeloma (MM) patients with regard to the expression of MPC-1, CD49e (VLA-5), and CD45: MPC-1(-)CD49e(-)CD45(+) proliferative immature cells, MPC-1(-)CD49e(-)CD45(-) immature myeloma cells, MPC-1(+)CD49e(-)CD45(-) and MPC-1(+)CD49e(-)CD45(+) intermediate myeloma cells, and MPC-1(+)CD49e(+)CD45(+) mature myeloma cells. We performed phenotypic analyses in 75 cases of monoclonal bone marrow plasmacytosis, including 46 cases of MM and 29 cases of monoclonal gammopathy of undetermined significance (MGUS). In 31 cases of progressive MM disease, MPC-1(-) immature and MPC-1(-)CD45(+) proliferative immature myeloma cells were significantly increased up to >25% and >10%, respectively, of the plasma cell fractions (CD38(++) cells), whereas there were no increases in MPC-1(-) or MPC-1(-)CD45(+) proliferative immature myeloma cells in 15 cases of stable disease. Interestingly, the proportions of MPC-1(-) and MPC-1(-)CD45(+) immature monoclonal plasma cells also increased in the 7 progressive cases of MGUS. Finally, we present the revised (2005) phenotypic classification of monoclonal marrow plasmacytosis (MOMP-2005).
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PMID:An increase in MPC-1- and MPC-1-CD45+ immature myeloma cells in the progressive states of bone marrow plasmacytosis: the revised phenotypic classification of monoclonal marrow plasmacytosis (MOMP-2005). 1644 50


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