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)

The expression of HLA class II molecules is mainly regulated transcriptionally and this regulation is thought to play an important role to the control of immune response. In this report, we have studied the effect of adenylate cyclase activator, forskolin, to the expression of HLA class II molecules on the cell surface of an human multiple myeloma cell line, RPMI8226. On the northern blot analysis and FACS analysis, we have revealed that forskolin upregulated the expression of mRNAs of DQB and DRB gene and their products on its surface. On the sequence analysis of upstream of HLA-DQB gene, we have identified not only Y-,X-, W-box, which were thought to regulatory region of truncated gene, but also cAMP responsible element (CRE) like regulatory region, which located upstream of W-box. On the gel retardation assay, when we used DNA probes that were specific for CRE like region and Y-box, we have found newly detectable bands, which appeared by forskolin treatment. These data suggest that forskolin upregulates HLA class II molecules by means of the interaction between CRE and cAMP responsible element binding protein (CREB).
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PMID:[Analysis of the regulation of HLA class II genes by forskolin]. 132 79

The TH line was established by bringing tumour cells from a multiple myeloma patient into suspension culture and subsequently cloning them by limiting dilution. The cultured cells show marked heterogeneity; there are ultrastructural differences between small and large TH cells, particularly with respect to the rough endoplasmatic reticulum (RER). Karyotyping revealed chromosome numbers in the triploid range, with many structural abnormalities, at the 14q32 region among others. A t(14;18) could not be demonstrated. TH was shown to have germline and a rearranged allele for kappa light chain, and only a single rearranged gene for heavy chain immunoglobulin. TH expressed PCA-1, CD9, CD28 and CD38 antigens, HLA class II, RER and kappa light chain, but few or no other antigens associated with the B-cell lineage. Light chain kappa and trace amounts of IgG3 were found intracellularly as well as in culture supernatant. The addition of IL-6 to cultures of TH increased proliferation, as well as the secretion of kappa light chain and the membrane expression of CD28 and CD38 antigens. Because TH has relatively few B cell markers on its membrane, it may be useful for the induction of monoclonal antibodies specific for human plasma cells. It also provides a model for the demonstration that IL-6 can act as a paracrine growth and differentiation factor for cells of myelomal origin.
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PMID:Characterization of a human plasmacytoma line. 195 80

Hybridization of murine myeloma cells P3-X63-Ag8.653 with splenocytes from a BALB/c mouse immunized with the syngeneic anti HLA-DR1,4,w6,w8,w9 MAb AC1.59 resulted in the development of 108 hybridomas secreting antiidiotypic antibodies. 100 of them inhibited the binding of MAb AC1.59 to target cells. Detailed analysis of the antiidiotypic MAb F5-444, F5-830, F5-963, F5-1126, F5-1336, and F5-1419 showed that all of them recognize idiotopes within or spatially close to the antigen combining site of MAb AC1.59. In cross-blocking experiments, the six antiidiotypic MAbs cross-blocked each other. It is likely that the six MAbs recognize spatially close, but not identical idiotopes because they elicited antiantiidiotypic antibodies of different or similar, but not identical specificity and differ in their ability to elicit anti-HLA class II antibodies. The latter, which were found only in sera from BALB/c mice immunized with antiidiotypic MAb F5-444 and F5-830, mimic the specificity of MAb AC1.59 and express the idiotope defined by the immunizing antiidiotypic MAb. These results indicate that the MAb F5-444 and F5-830 are antiidiotypes beta and the remaining four are antiidiotypes gamma.
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PMID:Murine antiidiotypic monoclonal antibodies that bear the internal image of HLA-DR allospecificities. 247 77

A monoclonal antibody (MAb), 13.3.B4, was obtained from a murine hybridoma after fusing Sp2/0 myeloma cells with spleen cells from C3H mice immunized with mouse L cells transfected with the A1 and B1 genes of HLA-DPw4. In radiobinding-assays, MAb 13.3.B4 bound to HLA transfectants expressing DPw2 or DPw4 as well as DPw2 or DPw4 homozygous B-cell lines, while most cell lines expressing other DP determinants were negative. MAbs with known DP or other HLA class II-specificities were used to inhibit binding of MAb 13.3.B4 in a radioimmunoassay. Three MAbs demonstrated inhibition, but their pattern of reactivity with HLA homozygous B cell lines differed from that of MAb 13.3.B4. An evaluation of DNA sequence data showed that MAb 13.3.B4 reacts with all cell lines expressing DP beta-chains of type 2.1, 2.2, 4.1 or 4.2. No correlation between 13.3.B4-reactivity and expression of DP alpha-chain variants was found. The results indicate that MAb 13.3.B4 defines a polymorphic epitope which may be determined by the sequence gly-gly-pro-met at residues 84-87 of the DP beta-chain.
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PMID:Characterization of a monoclonal antibody recognizing a polymorphic epitope mainly on HLA-DPw2 and DPw4 molecules. 248 51

To investigate whether B lymphocytes are involved in the malignant cell clone of multiple myeloma (MM), we performed immunoglobulin gene rearrangement analysis of mononuclear cells and separated B lymphocytes, isolated from bone marrow and peripheral blood of MM patients. The B lymphocytes were separated by immunomagnetic beads, coated with an HLA class II specific antibody. Southern blot analysis with a JH probe revealed in the bone marrow of three out of seven patients identical immunoglobulin gene rearrangements in the B lymphocytes when compared to the plasma cells. Out of 10 patients, two patients with a high tumour burden were found to have monoclonal B lymphocytes in the peripheral blood. These results suggest that B lymphocytes in the bone marrow are part of the myeloma clone and that they can circulate in the peripheral blood. Although previous studies indicated that the ratio of K to lambda bearing lymphocytes in the peripheral blood can provide evidence for B cell monoclonality, we did not find a correlation between the results of K/lambda analysis and immunoglobulin gene rearrangement.
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PMID:Detection of monoclonal B lymphocytes in bone marrow and peripheral blood of multiple myeloma patients by immunoglobulin gene rearrangement studies. 260 18

A human myeloma cell line designated LOPRA-1 has been established from ascites fluid containing malignant plasma cells of a patient with IgA2/kappa multiple myeloma. The cultured cells which are Epstein-Barr virus (EBV) negative have retained the morphological, cytochemical, ultrastructural and immunophenotypical features of well-differentiated plasma cells. They express the plasma cell antigen PCA-1, the antigens CD28 (Kolt-2) and CD38 (OKT10), the transferrin-receptor (OKT9), and some epitopes of the CD24 antigen (HB8, VIB E3), but are negative for surface immunoglobulins. HLA class II antigens (HLA-DP, -DQ, -DR) and other B-cell markers such as CD10 (CALLA), CD19 (B4), CD20 (B1), CD21 (B2), CD22 (HD39), CD23 (MHM6), CD37 (BL14) and CD39 (G28-8) as analysed by both flow cytometry and immunocytochemistry (PAP/APAAP). With respect to immunoglobulin synthesis, two stable clones were selected by single cell cloning: clone LOPRA-1/5 synthesizes large amounts of alpha 2 heavy and kappa light chains, but secretes only small amounts of these molecules, whereas clone LOPRA-1/4 is clearly devoid of intracellular immunoglobulin heavy and light chains and thus appears to be a chain loss variant. Cytogenetic analysis revealed a pseudotriploid phenotype with several structurally abnormal marker chromosomes: 3n + -, 70, XX, -X, -1, -4, -6, -8, -8, -13, -16, +7, +18, +21, +i(1q), +i(1q), +6q-, +3mar.
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PMID:Establishment and characterization of a permanent human IgA2/kappa myeloma cell line. 313 91

A monoclonal antibody-secreting hybridoma cell line, VCD-1, was derived from the fusion of murine myeloma cells with splenocytes from a BALB/c mouse that had been immunised with chronic B-lymphocytic leukaemia cells. The cells came from a patient who had developed the leukaemia approximately 10 years after a course of radiotherapy for nodular sclerosing Hodgkin's disease. The antibody bound to a 30,000-dalton protein that was present in normal and malignant B cells, in monocytes, neutrophils, and interdigitating reticulum cells, and in malignant cells present in Hodgkin's disease lymph nodes. The reactive epitope was not accessible to antibody in viable intact cells; binding to peripheral blood cells could only be seen if the cells were fixed. The antibody recognises a determinant that probably resides on the alpha-chain of HLA class II molecules.
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PMID:A monoclonal antibody to an antigen present in cells from a patient with Hodgkin's disease. 331 34

There is still much controversy about the precursor cell type in multiple myeloma (MM). Some authors claim that it is a pre-B cell, others state that it is a memory B cell or plasmablast. We have recently shown that the VDJ region of the MM immunoglobulin heavy chain gene is somatically hypermutated and antigen selected, without intraclonal variation or evolution in time. By using a patient-specific PCR approach we have now obtained evidence that the premyeloma cell can be situated in the pre-switched B-cell compartment and that heavy chain switching can occur without further somatic mutation. Based on the MM immunoglobulin sequences derived from the bone marrow, patient-specific CDR2 and CDR3 oligonucleotides were designed. B lymphocytes were separated from plasma cells based on the expression of CD19 and HLA class II or surface bound IgM using immunomagnetic beads. The expressed Ig sequences were amplified by RT-PCR using patient specific CDR2 primers and isotype specific primers (C mu, C gamma, and C alpha). Myeloma-specific Ig sequences were detected by a myeloma-specific CDR3 probe and sequenced. In one out of five cases we found in the peripheral blood clonally related IgM and IgA sequences with the same somatic mutations as the MM-IgG sequence. In another case of an IgG MM we found in the bone marrow clonally related IgA sequences with the same somatic mutations. These findings, together with the fact that myeloma-Ig genes contain somatic mutations without intraclonal variation, suggest that the clonogenic cell in multiple myeloma can originate from a pre-switched but somatically mutated B cell.
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PMID:Evidence that the clonogenic cell in multiple myeloma originates from a pre-switched but somatically mutated B cell. 794 57

We recently found that sperm protein 17 (Sp17), a spermatozoa-restricted protein, is aberrantly expressed on the tumor cells in patients with multiple myeloma (MM). It may therefore be possible to generate donor-derived Sp17-specific CTL for administration following allogeneic stem cell transplant to augment graft-versus-myeloma (GVM) effect without inducing a global GVHD. To assess this approach, we have produced recombinant Sp17 protein and used Sp17 protein-pulsed dendritic cells to generate HLA class I-restricted Sp17-specific CTL from a previously unimmunized healthy donor. These CTL were able to lyse autologous Epstein-Barr virus-transformed lymphoblastoid cells in a Sp17-dependent manner. Target lysis was HLA-A1 and HLA-B27 restricted. Cytotoxicity could be blocked by antibodies against monomorphic HLA class I, HLA-A1 and HLA-B27 molecules but not HLA class II molecules. Most importantly, the CTL lysed HLA class I-matched Sp17-positive tumor cells, suggesting that Sp17 is processed and presented in association with the HLA class I molecules in Sp17-positive tumor cells in a concentration and configuration that could be recognized by recombinant protein-primed CTL. Analysis by flow cytometry of the CTL indicated that they were predominantly CD8 in phenotype and they produced IFN-gamma and very little IL-4. Our results suggest the potential for the generation and administration of donor-derived Sp17-specific CTL to augment GVM without inducing GVHD following allogeneic stem cell transplant for MM.
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PMID:Sperm protein 17 (Sp17) in multiple myeloma: opportunity for myeloma-specific donor T cell infusion to enhance graft-versus-myeloma effect without increasing graft-versus-host disease risk. 1147 39

Following a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT), minor histocompatibility antigens (mHags) play an important role in the induction of graft-versus-leukaemia (GvL) and graft-versus-myeloma (GvM). Many mHags show ubiquitous tissue expression and are associated with GvL and graft-versus-host disease. Here we describe a cytotoxic CD4(+) T lymphocyte line and a cytotoxic, CD4(+) T cell clone (CTC), 3AB11, which recognized a tissue-restricted mHag. This CTC was isolated from a multiple myeloma patient with clinical GvM following an HLA-matched allo-SCT. CTC 3AB11 was activated in a HLA-DP*0401 restricted fashion and the antigen was expressed by 27% of HLA-DP*0401 positive Epstein-Barr virus (EBV)-transformed B-cell lines (EBV-B). Tissue distribution analysis of antigen 3AB11 showed it to be expressed by patient-derived EBV-transformed B cell lines (EBVp), the myeloma plasma cell-line UM9 and monocytes. It was weakly expressed by peripheral blood-derived phytohaemagglutinin-induced T-cell blasts and absent on CD40L stimulated peripheral B (CD40L B) cells and stromal cells. The relatively high prevalence of the HLA class II-restricted 3AB11 antigen, together with its apparent haematopoietic-restricted expression, makes it an antigen of interest for cellular immunotherapy.
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PMID:A class II-restricted cytotoxic T-cell clone recognizes a human minor histocompatibility antigen with a restricted tissue distribution. 1560 52


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