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 plasma cells of patients with myeloma are frequently aneuploid, have a high RNA content and typically show monoclonal immunoglobulin in their cytoplasm. Kappa-lambda co-expression in aneuploid tumor cells was restricted to patients with IgG lambda myeloma. Immunophenotype studies revealed early B cell expression often in association with mature B cell markers. Chromosomal aberrations were complex with a predominance of numeric but also structural lymphoma-type translocations; the latter were most prevalent in IgA myeloma. Specific translocations such as t(8;14) and t(11;14) were accompanied by aberrations of c-myc and bcl-l cellular genes. Effective salvage programs have been developed for melphalan-prednisone refractory myeloma. In comparing high-dose dexamethasone with vincristine-adriamycin + dexamethasone (VAD), VAD was superior particularly for relapsing myeloma (response rate of 60 vs. 23%). For VAD refractory myeloma, high-dose melphalan (HDM) programs were developed; total body irradiation (850 rad) followed by HDM 140 mg/m2 and supported by autologous bone marrow grafts was particularly effective and relatively well tolerated with all 4 patients still in remission from 3 to 15 months.
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PMID:Biology and therapy of multiple myeloma. 312 42

A human-mouse myeloma analogue termed HMMA2.11TG/O was constructed by fusion of the mouse myeloma cell line P3x63Ag8.653, a mutant derivative of MOPC21, with bone marrow mononuclear cells from a patients with IgA myeloma. The HMMA2.11TG/O cell line is resistant to 6-thioguanine and ouabain and sensitive to HAT. The cell line secretes no detectable immunoglobulin and has a hybrid karyotype and cell surface phenotype. An average fusion efficiency for growth of hybridomas of 1/17,000 fused cells was obtained in fusions with human peripheral blood mononuclear cells (PBM), Pokeweed Mitogen (PWM) stimulated PBM, and Epstein-Barr Virus (EBV) transformed polyclonal B cell lines. Over 75% of hybrids secrete detectable immunoglobulin and the cloning efficiency of the hybrids at 1 cell/well averages 25%. Antibody secreting cloned hybridoma cell lines were obtained by fusion directly with PBM from an immunized volunteer and by fusion with in vitro, secondarily immunized, EBV transformed polyclonal cell lines. Five hybridomas secreting human monoclonal IgM anti-tetanus antibodies and 2 secreting human monoclonal IgG anti-tetanus antibodies were selected and cloned from 6 fusions performed specifically for anti-tetanus antibody. Immunoglobulin and antibody secretion by cloned hybrids has been stable for 5-10 months at present. Immunoglobulin and antibody secretion in routine cultures passaged every 3-4 days has been 8-42 micrograms/ml. This human-mouse myeloma analogue should prove useful for the routine production of human monoclonal antibodies.
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PMID:The construction and use of a human-mouse myeloma analogue suitable for the routine production of hybridomas secreting human monoclonal antibodies. 343 25

To determine the extent of clonal involvement of the secretory immune system and the origin of salivary immunoglobulins (Ig) in monoclonal gammopathy patients, saliva and serum samples were collected from five affected individuals (two IgA myelomas, one IgG myeloma, one IgG benign monoclonal gammopathy, and one IgM lymphoma) and were assayed for the presence of monoclonal Ig. Purified polyclonal or monoclonal anti-idiotype (Id) antibodies were prepared against each of the isolated serum paraproteins. In all five individuals, the patient saliva samples inhibited the binding of 125I-labeled homologous Ig to the corresponding anti-Id antibodies, but normal saliva did not. The concentration of Id in patients' saliva varied from 1 to 400 micrograms/ml; i.e., 0.004 to 1.0% of the corresponding serum values. Saliva of a lymphoma patient whose IgM kappa protein exhibited rheumatoid factor (RF) activity also contained RF. The salivary Id-bearing molecules were found to have the same Ig isotype as the serum paraproteins. The myeloma IgA represented a minor component (0.4 and 3.9%) of the total salivary IgA. The salivary IgA myeloma proteins were associated at least in part with secretory component, but the salivary IgG paraproteins were not. In an IgA myeloma patient, a minority (17%) of the IgA+ plasma cells found in the lacrymal gland biopsy specimen were Id+, whereas the great majority (98%) of bone marrow IgA plasma cells were Id+. The results suggest active transport rather than passive transudation of myeloma IgA into the patients' saliva, and the integrity of the secretory immune system was not compromised by the neoplastic process.
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PMID:Analysis of paraprotein transport into the saliva by using anti-idiotype antibodies. 379 39

We have previously demonstrated that 1) BALB/c mice and patients with IgA myeloma developed a marked expansion of T cells with surface IgA-Fc receptors (T alpha cells), 2) the FcR alpha were induced by direct interaction of soluble myeloma IgA with T cells, and 3) the T alpha cells induced in IgA myeloma were Lyt-1-2+, IgA isotype-specific suppressor cells in normal immune responses. These findings established that the host with IgA myeloma responds to the large amounts of Ig produced by the tumor by activating an otherwise normal IgA isotype-specific suppressor circuit. In the present studies, we extend our previous observations and show that T alpha cells can suppress both the growth and secretion of MOPC-315 myeloma tumor cells. Thus, the isotype-specific immunoregulatory circuit activated in myeloma is capable of suppressing tumor cells as well as normal cells.
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PMID:T cells with FC receptors in myeloma; suppression of growth and secretion of MOPC-315 by T alpha cells. 387 Nov 17

The level of IgA-alpha 1 anti-trypsin (alpha 1 AT) complex in a relatively large number of IgA myeloma sera has been determined, and compared with their content of polymerised forms of IgA. The level of the complex was the same in sera containing only monomeric IgA, some polymer and more than 50% polymer (as determined by SDS-PAGE). There was, however, a highly significant inverse correlation between the amount of IgA-alpha 1 AT complex in the myeloma sera and their content of 10S dimer (as determined by analytical ultracentrifugation). High levels of IgA-alpha 1 AT complex were also found in the small number of myeloma sera examined which contained paraprotein of the minor allotypic form of (Am2+) of the IgA2 sub-class, indicating that the lack of disulphide bonds between the heavy and light chains of this isotype has no influence on its ability to complex with alpha 1 AT.
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PMID:Measurement of IgA-alpha 1 anti-trypsin (alpha 1 AT) complex in the sera of patients with IgA myelomatosis. 387 38

The authors describe a new case of subcorneal pustular dermatosis associated with IgA myeloma. The significance of this association is unknown, but it seems to be more than a coincidence. The case described is particular, because the interval between skin eruption and first symptoms of myeloma is very long (27 years), and palms and soles are involved.
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PMID:Subcorneal pustular dermatosis and IgA myeloma. 389 37

A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.
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PMID:Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma. 404 68

Eight IgA myeloma proteins derived from independently induced plasma-cytomas in genetically similar inbred BALB/c mice are functionally related by their binding of phosphoryl choline-containing antigens (Pneumococcus C polysaccharide or Lactobacillus antigen). Each protein resembles a single species of immunoglobulin in antibody. The proteins are characterized by highly sensitive myeloma-specific antisera prepared by immunizing mice of other inbred strains with the BALB/c myeloma proteins. Individual or myeloma-specific determinants located on Fab fragments were found on three of the proteins that were unique for that protein and did not react with any other IgA protein among over 70 tested. Remarkably, five of the proteins shared two common myeloma-specific determinants which were specific for this group of five proteins. These results suggest that the five functionally and genetically related proteins sharing the same myeloma-specific determinants might also be structurally similar.
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PMID:Common individual antigenic determinants in five of eight BALB-c IgA myeloma proteins that bind phosphoryl choline. 410 63

Rabbit antiserum was prepared against mouse myeloma Protein-315, an IgA protein with specificiy toward the 2,4-dinitrophenyl group. After absorption of the antiserum with another IgA myeloma protein and with affinity-labeled Protein-315, the antiserum was specific for idiotypic determinants on Protein-315. Monovalent ligands that bind to Protein-315 with high affinity strongly inhibited the reaction of the protein with its anti-idiotypic antiserum. This indicated that the region of the hapten-binding site is a major idiotypic determinant. The myeloma protein is thus similar to rabbit antibenzoate antibody in this respect. These results, considered in conjunction with other data in the literature, indicate that an anti-idiotypic antiserum prepared in an isologous or heterologous species can recognize the same determinant, in this case the region comprising the ligand-binding site. Quantitative aspects of the data indicate that there is competition between the hapten and antiidiotypic antibodies for the site.
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PMID:Reaction of anti-idiotypic antibody with the hapten-binding site of a myeloma protein. 410 73

Two H-2-linked autosomal dominant immune response (Ir) genes Ir-IgG and Ir-IgA were demonstrated to be at separate loci. Ir-IgG controls the immune response to IgG (gamma2a) myeloma proteins and Ir-IgA the immune response to IgA meyloma proteins. Both genes are associated with the H-2K region specificities of the H-2 chromosome, specifically Ir-IgG with H-2(b) and Ir-IgA with H-2(a). Different recombinants derived from H-2(a)/H-2(b) crossovers were examined for their immune responsiveness to BALB/c IgG (gamma2a) and IgA myeloma proteins. B10 (H-2(b)) parental type responded only to IgG; B10.A (H-2(a)) responded only to IgA. All the recombinants except for B10.A (4R) responded to either IgG or IgA. B10.A (4R), however, responded to both IgG and IgA. This indicated that the crossover event giving rise to B10.A (4R) occurred between the Ir-IgG and Ir-IgA loci.
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PMID:H-2-linked immune response (Ir) genes. Independent loci for Ir-IgG and Ir-IgA genes. 411 90


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