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)

Sera, purified myeloma proteins, and urinary proteins obtained from eight patients with igA multiple myeloma were studied by physical-chemical and immunochemical methods. In six patients whose serum viscosity was increased, the sedimentation constants of the principal component of myeloma proteins ranged from 9.1 to 10.2 S. In two patients with nearly normal serum viscosity, the sedimentation constants of these proteins were 6.2 and 7.2 S. IGA-albumin complexes were detected in most of the sera, but invarying amounts; no complexes of ig with amylase, secretory component, or alpha(1)-antitrypsin were observed. Studies on isolated myeloma proteins revealed that all igA proteisn from sera with increased viscosity represented true polymers, linked by disulfide bonds, rather than noncovalently associated aggregates; J chain was detecable by both alkaline-urea disc electrophoresis and immunoelectrophoresis with a monospecific anti-J chain serum. Increased serum viscosity was not related to the igA subclass, L chain type, or the carbohydrate compositions of individual igA myeloma proteins. The urine of five patients contained free light chains corresponding in type to the light chain of the particular igA myeloma protein. However, free J chain was not detected. The immunoelectrophoretic analysis for the presence of J chain in sera of myeloma patients may be used for early and simple detection of polymeric forms of myeloma proteins.
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PMID:Properties of IgA myeloma proteins isolated rom sera of patients with the hyperviscosity syndrome. 40 74

The mouse mb-1 gene was originally identified based on its restricted expression in B lineage cells. Predicted structural homology with the gamma chain of the CD3 complex on T cells led to the suggestion that the MB-1 protein might associate with surface Ig(sIg) on B cells and be involved in signal transduction. Other studies identified at least two proteins that are noncovalently associated with sIgM, one of which has recently been shown to be the product of the mb-1 gene. To identify genes specifically expressed in normal human B cells we constructed a B minus T lymphocyte subtraction library and isolated a cDNA clone highly homologous to murine mb-1 (m-mb-1). A full-length cDNA was subsequently isolated and found to encode a membrane glycoprotein of 226 amino acids. It included a leader sequence (32 amino acids), an extracytoplasmic domain (111 amino acids) containing six potential N-glycosylation sites and three cysteine residues for potential inter- or intrachain disulfide linkages, a transmembrane domain (22 amino acids), and an intracytoplasmic domain (61 amino acids). The amino acid sequence homology between human and mouse mb-1 was especially striking (approximately 92%) in the intracytoplasmic, transmembrane, and membrane-proximal extracellular domains but was less marked (approximately 42%) in the remaining extracytoplasmic portion. Interestingly, part of the 3'-untranslated region was also highly conserved between species, suggesting an important role for this region in the regulation of mb-1 expression. The human mb-1 (h-mb-1) cDNA hybridized with a mRNA species of approximately 1.2 kb on Northern blots. Similar to m-mb-1, the h-mb-1 transcripts could be detected in pre-B cell lines and fetal bone marrow, in normal, mitogen activated- and transformed B cells but not in myeloma plasma cells. h-mb-1 was not expressed in peripheral T cells nor by cells of other hemopoietic lineages or in brain, heart, muscle, lung, and kidney. Surprisingly, however, low levels of h-mb-1 transcripts were detectable in two early T lineage cell lines and in the fetal thymus. This suggests that mb-1 may have other functions in addition to its role in signal transduction in B lineage cells.
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PMID:Molecular cloning and expression pattern of a human gene homologous to the murine mb-1 gene. 153 35

To establish the clonal origin of a case of concomitant B-cell chronic lymphocytic leukemia (IgM kappa) and multiple myeloma (IGA lambda), we analyzed the immunoglobulin (Ig) gene rearrangements in the patient's blood and bone marrow. Despite the different isotypes, pretreatment investigation of the heavy chain gene (JH) revealed a germline fragment and two identical rearrangements in the blood and marrow. Both kappa and lambda light-chain genes were rearranged in the blood, suggesting peripheral blood lymphocyte involvement in the myeloma. Analysis of the Ig genes after chemotherapy demonstrated no change in the JH or CK rearrangements; however, the lambda genes were now in a germline configuration. Our results suggest that in this patient both chronic lymphocytic leukemia and myeloma originated from the same B-cell progenitor.
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PMID:Molecular evidence for a single clonal origin in biphenotypic concomitant chronic lymphocytic leukemia and multiple myeloma. 280 47

Primary plasmacytoma of the lymph nodes is very rare, and there are fewer than 20 reported cases. These cases appeared to have a better prognosis than other extramedullary plasmacytomas, with rare recurrence and no progression to myeloma after treatment. To better characterize the clinicopathological features and the pathogenesis of primary plasmacytoma of the lymph nodes, we reviewed our consultation files and retrieved seven such cases. The age of presentation ranged from 39 to 76 years (median age, 59 years), with three women and four men. The clinical follow-up varied from 1 to 14 years. All patients presented with enlarged lymph nodes and had an indolent clinical course, except for one patient with slow progression and increasing numbers of bone marrow plasma cells. Five patients were treated with excision only and two with excision and chemotherapy. None of the patients had recurrence or developed multiple myeloma. All cases showed immunoglobulin light chain restriction, four with monotypic lambda and three with monotypic kappa. One patient had extensive nodal amyloid deposition. Four cases had monoclonal heavy chain expression, three with monoclonal immunoglobulin (Ig) G and one with monoclonal IgM. All cases were negative for CD20 and CD43, and six cases expressed CD79a. Overexpression of p53 and bcl-2 was not detected by immunostaining in any of the cases. Epstein-Barr viral (EBV) RNA was not detected in all seven cases by in situ hybridization, and no Kaposi's sarcoma-associated herpesvirus (KSHV) DNA sequences were detected by polymerase chain reaction in five cases. Our results confirm a more favorable outcome and rare progression to multiple myeloma in primary nodal plasmacytomas after excision or chemotherapy. The results of oncoprotein and viral studies suggest that the pathogenesis of primary nodal plasmacytoma may not be due to bcl-2- and p53-associated changes or viral-induced changes by EBV and KSHV.
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PMID:Primary plasmacytoma of lymph nodes. 930 34

The nature of the proliferating fraction in myeloma is still not known and understanding the characteristics of this fraction is central to the development of effective novel therapies. However, myeloma plasma cells typically show a very low rate of proliferation and this complicates accurate analysis. Although the level of CD45 and/or VLA-5 has been reported to identify proliferating 'precursor' plasma cells, there are discrepancies between these studies. We have therefore used a rigorous sequential gating strategy to simultaneously analyse cycle status and immunophenotype with respect to CD45, VLA-5 and a range of other integrin molecules. In 11 presentation myeloma patients, the proliferative fraction was distributed evenly between CD45+ and CD45- cells, however, cycling plasma cells were consistently VLA-5-. There was close correlation between the expression of VLA-5 and a range of other integrin molecules (CD11a, CD11c, CD103), as well as the immunoglobulin-associated molecules CD79a/b (Spearman, n = 10, P < 0.0001). In short-term culture, cells that were initially VLA-5-showed increasing VLA-5 expression with time. However, simultaneous analysis of the DNA-binding dye 7-amino-actinomycin D demonstrated that this was not as a result of differentiation, as VLA-5+ plasma cells were all non-viable. This was confirmed in freshly explanted plasma cells from nine patients. Discrete stages of plasma cell differentiation could not be distinguished by the level of CD45 or VLA-5 expression. The results indicate that there is a single stage of plasma cell differentiation, with the phenotype CD38+CD138+VLA-5-. These findings support the hypothesis that neoplastic bone marrow plasma cells represent an independent, self-replenishing population.
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PMID:In multiple myeloma, only a single stage of neoplastic plasma cell differentiation can be identified by VLA-5 and CD45 expression. 1191 67

An uncommon manifestation of plasma cell neoplasia occurs outside the bone marrow and is designated "extramedullary plasmacytoma." These are usually encountered in mucosal sites of the head and neck region. The gastrointestinal tract may be secondarily involved in multiple myeloma or be the site of primary extramedullary plasmacytomas (PEMPs). The esophagus is the least common site of gastrointestinal PEMP. A 58-year-old man presented with dysphagia for solids over a period of 2 months. Otherwise, he was well and systemic examination did not reveal anything of note. After a nondiagnostic biopsy, the patient was subjected to esophago-gastrectomy. Gross examination of the esophagus revealed a large polypoid tumor. Histologically, it was composed of mature plasma cells, plasmablasts (some of which appeared anaplastic), and a minor admixture of lymphoid cells. Focally, the infiltrate permeated the squamous epithelium simulating lymphoepithelial lesions. The neoplastic cells were positive for epithelial membrane antigen, CD79a, IgG, and kappa, while the lymphoid cells were predominantly B cells. The patient did not have a monoclonal gammopathy. Skeletal x-rays and bone trephine examination were both normal. PEMP is biologically and prognostically different to other plasma cell neoplasms. Although rare, esophageal PEMP should be considered in the differential diagnosis of so-called undifferentiated malignant tumors of the esophagus.
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PMID:Primary extramedullary plasmacytoma of the esophagus. 1280 70

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

Plasmablastic lymphoma was initially described as a variant of diffuse large B-cell lymphoma (DLBCL) involving the oral cavity of HIV+ patients and characterized by immunoblastic morphology and a plasma cell phenotype. However, other lymphomas may exhibit similar morphologic and immunophenotypic features. To determine the significance of plasmablastic differentiation in DLBCL and examine the heterogeneity of lymphomas with these characteristics, we examined 50 DLBCLs with low/absent CD20/CD79a and an immunophenotype indicative of terminal B-cell differentiation (MUM1/CD38/CD138/EMA-positive). We were able to define several distinct subgroups. Twenty-three tumors were classified as plasmablastic lymphoma of the oral mucosa type and showed a monomorphic population of immunoblasts with no or minimal plasmacytic differentiation. Most patients were HIV+ and EBV was positive in 74%. Eleven (48%) cases presented in the oral mucosa, but the remaining presented in other extranodal (39%) or nodal (13%) sites. Sixteen cases were classified as plasmablastic lymphoma with plasmacytic differentiation. These were composed predominantly of immunoblasts and plasmablasts, but in addition exhibited more differentiation to mature plasma cells. Only 33% were HIV+, EBV was detected in 62%, and 44% had nodal presentation. Nine cases, morphologically indistinguishable from the previous group, were secondary extramedullary plasmablastic tumors occurring in patients with prior or synchronous plasma cell neoplasms, classified as multiple myeloma in 7 of the 9. Two additional neoplasms were an HHV-8+ extracavitary variant of primary effusion lymphoma and an ALK+ DLBCL. HHV-8 was examined in 39 additional cases, and was negative in all. In conclusion, DLBCLs with plasmablastic differentiation are a heterogeneous group of neoplasms with different clinicopathological characteristics that may correspond to different entities.
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PMID:Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. 1516 65

We generated a murine monoclonal antibody (B28p) detecting an antigenic determinant shared by the immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) receptor (the immunogen used to raise B28p) and an unrelated 28-kDa protein that was subsequently subjected to extensive characterization. The expression of the 28-kDa protein in normal lymphohematopoietic tissues was restricted to B cells and plasma cells and clearly differed from that expected for IRTA1 (selectively expressed by mucosa-associated lymphoid tissue [MALT] marginal zone B cells). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (TPD52), whose expression had been previously described only in normal and neoplastic epithelia. Specific B28p reactivity with TPD52 was confirmed by immunostaining/immunoblotting of TPD52-transfected cells. TPD52 expression pattern in normal and neoplastic B cells was unique. In fact, unlike other B-cell molecules (paired box 5 [PAX5], CD19, CD79a, CD20, CD22), which are down-regulated during differentiation from B cells to plasma cells, TPD52 expression reached its maximum levels at the plasma cell stage. In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca(2+)-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells. Finally, the anti-TPD52 monoclonal antibody served as a valuable tool for the diagnosis of B-cell malignancies.
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PMID:Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca(2+)-dependent association with annexin VI. 1557 73

The present case involves unique enteritis forming multiple ulcers associated with Epstein-Barr virus (EBV). A 57-year-old man had undergone a reduced intensity allogeneic stem cell transplantation for a relapse of multiple myeloma following sequential autologous peripheral blood stem cell transplantation. The ileum, resected for massive melena, showed multiple irregular ulcers with occasional cobblestone-like appearance. There was inflammation including numerous plasma cells in the ulcer bases and surrounding areas, where many EBV-infected plasma cells were detected by double staining with EBV-encoded small RNA-1 (EBER-1) in situ hybridization and CD79a, while EBV-infected epithelial cells were not noted. The number of EBER-1-positive cells in the ileum (mucosa, 1451 cells/mm(2); submucosa, 465 cells/mm(2)) was much larger than in control samples (malignant lymphoma or leukemia after allogeneic stem cell transplantation, n = 4, range 0-113 cells/mm(2); malignant lymphoma after chemotherapy, n = 14, range 0-0.89 cells/mm(2); colon cancer, n = 12, range 0-3.5 cells/mm(2)). In the mucosa near the ulcers, EBER-1-positive cells often surrounded and involved the glandular epithelium, forming lymphoepithelial-like lesions. The histological findings differ from post-transplant lymphoproliferative disorders or intestinal thrombotic microangiopathy, and this is the first case of EBV-associated enteritis with ulcers characterized by numerous plasma cells and lymphoepithelial-like lesions after stem cell transplantation.
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PMID:Epstein-Barr virus-associated enteritis with multiple ulcers after stem cell transplantation: first histologically confirmed case. 1693 Mar 33


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