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)

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the beta2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.
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PMID:Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. 1061 Jan 15

Although expression of CD95 (Fas/Apo-1) on myeloma cells has been reported, its significance is not clearly understood. We established a myeloma cell line, KHM-11ad (11ad), from a parental cell line, KHM-11, by collecting cells adhered to a plastic dish. KHM-11 cells have been reported to be positive for CD45 and CD95 (Fas/Apo1), and negative for a myelomonocytic antigen, CD13. Interestingly, CD95 was not detected in 11ad. Expression of CD45 was also significantly decreased in 11ad cells while expression of CD13 was detected in these cells. The growth rate of 11ad cells was 1.7 times lower than that of KHM-11 cells. Analysis of adhesion molecules showed that expression of VLA4 and CD44 was significantly suppressed in 11ad. The IC50 of melphalan (L-PAM) for 11ad cells was 50 times higher than that for KHM-11, indicating that 11ad is significantly refractory to L-PAM than KHM-11 cells. Induction of apoptosis by doxorubicin and cycloheximide was suppressed in 11ad cells compared with those in KHM-11 cells. Western blot analysis for Bcl-2 family of proteins showed that Bax was expressed at a 2.2 times lower level in 11ad cells than in KHM-11 cells while there was no difference in expression of Bcl-2, Bcl-Xs nor Bcl-XL. These results suggest that CD95-negative myeloma cells may have characteristics as follows: (1) slow proliferation; (2) low sensitivity to apoptosis; (3) low expression of VLA4, CD44 and Bax. Although these intraclonal variations were based on the findings of cell lines, these may reflect similar variations in vivo. The 11ad line may be a suitable model for analyzing intraclonal variation of myeloma cells.
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PMID:Establishment and characterization of a CD95 (Fas/Apo-1)-negative myeloma cell line. 1035 28

Human Herpesvirus 8 (HHV-8) is clearly associated with Kaposi's sarcoma (KS), body cavity-based lymphomas (BCBL), and certain forms of multifocal Castleman's disease (MCD). It appears to be the sexually transmissible agent involved in the development of AIDS-associated KS. HHV-8 genomes are invariably present in BCBL-derived cell lines where lytic replication of the virus can be induced by phorbol esters (PE). First-generation HHV-8 serological assays were based on these cell lines. More recently, several genes encoding HHV-8 antigens have been identified. One of the most reactive antigens is encoded by HHV-8 open reading frame K8.1. Although K8.1 does not exhibit overt sequence homology to any other known gene, it is likely to be analogous to gp220/350 of Epstein-Barr or gp150 of murine herpesvirus-68, virion-envelope glycoproteins involved in target cell recognition. Mice were immunized with purified GST-K8.1 fusion protein expressed in E. coli. After fusion of murine plasma cells with the myeloma cell line P3-X63-Ag8. monoclonal antibodies (MAbs) were generated, which are specifically directed against K8.1 protein. The binding site for each MAb was identified by deletion mutant analysis using recombinant GST-K8.1 mutants and K8.1-specific peptides. Without exception, the epitopes recognized by these MAbs were located within the N-terminal part of the protein [amino acids (aa) 29 to 80], thus identifying a highly immunogenic region. These antibodies will not only be useful tools for HHV-8 diagnostics, but will also facilitate the analysis of K8.1 function.
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PMID:Generation of monoclonal antibodies directed against the immunogenic glycoprotein K8.1 of human herpesvirus 8. 1100 1

Plasmacytomas are localized neoplastic proliferations of monoclonal plasma cells. When multifocal, the process is referred to as multiple myeloma. These lesions exhibit a pattern of antigen expression and cytomorphology that usually leads to a ready diagnosis. However, potentially troublesome variations in immunophenotype occur. We describe a case of a plasmacytoma from a patient who presented with sudden onset of pain and a lytic lesion of the left proximal humerus. Hematoxylin and eosin-stained sections showed a lymphoproliferative lesion composed of large lymphoid cells, some with plasmacytoid and immunoblastic features. The lesion also showed significant mitotic activity. Immunohistochemical staining was positive for CD45 (LCA), CD56 (N-CAM), CD43 (MT1), and cytokeratin CAM5.2. There was also clonal staining for lambda light chains. In addition, flow cytometric analysis showed positivity for myeloid markers such as CD13, CD33, CD38, and CD138. Significant negative markers include CD20 (L26), CD45RO (UCHL-1), and CD79alpha. The unusual phenotypic features of this plasmacytoma illustrate potential diagnostic pitfalls. It is important to fully study such lesions to correctly classify them, because this has significant impact on prognosis and management.
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PMID:Plasmacytoma with aberrant expression of myeloid markers, T-cell markers, and cytokeratin. 1137 26

This article describes the first case of acute myeloid leukemia (AML) in a healthy donor at 14 months after granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cell (PBSC) harvest. In September 2001, a healthy 61-year-old female was given G-CSF prior to PBSC harvest for her brother with multiple myeloma. In spite of successful engraftment, the recipient died from a disease relapse. In November 2002, the donor, admitted with high fever and leukocytosis with 98.5% blastoid cells, was diagnosed as having AML (M1). Her leukemia cells were positive for CD13, CD33, and G-CSF receptor without chromosomal abnormality and responded to G-CSF in vitro. During chemotherapy, she died of progressive pneumonia. If our case is truly the first, the incidence of leukemia in donors may not be higher than that of naturally occurring leukemia. However, efforts towards an international long-term study, or at least to report every case similar to ours, would be required to be conclusive.
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PMID:Acute myelogenous leukemia in a donor after granulocyte colony-stimulating factor-primed peripheral blood stem cell harvest. 1471 37

A 70-year-old woman presented with pancytopenia associated with plasma cell infiltration of her bone marrow. The plasma cells were often multinucleated and demonstrated phagocytosis of erythroid and granulocytic cells. Atypical immunophenotypic features included the expression of CD117 and CD13 and the lack of expression of CD56. Although kappa chains were demonstrable in the cytoplasm, no paraprotein was found in the serum or urine. Osteolytic lesions were absent. The pancytopenia of this unusual patient with non-secretory, hemophagocytic myeloma has improved on dexamethasone monotherapy, although her hemophagocytosis persists.
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PMID:Hemophagocytic, non-secretory multiple myeloma. 1529 68

We reported a case of multiple myeloma, who suffered from the acute myelomonocytic leukemia (AML-M4) after the chemotherapy of alkylating agent. The patient had a history of multiple myeloma and was treated with the regimen of including L-Sarcolysinum and cyclophosphamide for 5 years. The multiple myeloma of this patient was proved to have got the remission through bone marrow aspiration, immunofixation electrophoresis of serum, serum protein electrophoresis and detection of urine light chain. However, a pancytopenia of unknown cause was verified to peripheral blood. During the course of supportive treatment only with blood cell and platelet transfusion, WBC count of this patient showed a rising trend and the blast cells (8%-15%) started to occur in the peripheral blood. The further examination discovered that the ratio of blast cell was beyond 30% in bone marrow smear, and the flow cytometry detected the CD45, HLA-DR, CD13, CD33, CD64 to have the positive expressions. Thus, the diagnosis of multiple myeloma in remission and secondary AML-M4 was established. When the chemotherapy regimen to AML was being planned for this patient, she died of massive hemorrhage of gastrointestinal tract due to thrombocytopenia and ineffectiveness.
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PMID:[Acute myelomonocytic leukemia occurred after multiple myeloma treated: a case report]. 1744 63

Angiogenic growth factors induce the transcription of the cell surface peptidase CD13/APN in activated endothelial cells of the tumor vasculature. Inhibition of CD13/APN abrogates endothelial invasion and morphogenesis in vitro and tumor growth in vivo suggesting a critical functional role for CD13 in angiogenesis. Experiments to identify the transcription factors responsible for this regulation demonstrated that exogenous expression of the proto-oncogene c-Maf, but not other bZip family members tested, potently activates transcription from a critical regulatory region of the CD13 proximal promoter between -115 and -70 bp which is highly conserved among mammalian species. Using promoter mutation, EMSA and ChIP analyses we established that both endogenous and recombinant c-Maf directly interact with an atypical Maf response element contained within this active promoter region via its basic DNA/leucine zipper domain. However full activity of c-Maf requires the amino-terminal transactivation domain, and site-directed mutation of putative phosphorylation sites within the transactivation domain (serines 15 and 70) shows that these sites behave in a dramatic cell type-specific manner. Therefore, this atypical response element predicts a broader range of c-Maf target genes than previously appreciated and thus impacts its regulation of multiple myeloma as well as endothelial cell function and angiogenesis.
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PMID:CD13/APN transcription is regulated by the proto-oncogene c-Maf via an atypical response element. 1789 90

The interleukin-12 (IL-12) receptor (R) B2 gene acts as tumor suppressor in human acute and chronic B-cell leukemias/lymphomas and IL-12rb2-deficient mice develop spontaneously localized plasmacytomas. With this background, we investigated the role of IL-12R beta 2 in multiple myeloma (MM) pathogenesis. Here we show the following: (1) IL-12R beta 2 was expressed in primary MM cells but down-regulated compared with normal polyclonal plasmablastic cells and plasma cells (PCs). IL-6 dampened IL-12R beta 2 expression on polyclonal plasmablastic cells and MM cells. (2) IL-12 reduced the proangiogenic activity of primary MM cells in vitro and decreased significantly (P = .001) the tumorigenicity of the NCI-H929 cell line in SCID/NOD mice by inhibiting cell proliferation and angiogenesis. The latter phenomenon was found to depend on abolished expression of a wide panel of proangiogenic genes and up-regulated expression of the antiangiogenic genes IFN-gamma, IFN-alpha, platelet factor-4, and TIMP-2. Inhibition of the angiogenic potential of primary MM cells was related to down-regulated expression of the proangiogenic genes CCL11, vascular endothelial-cadherin, CD13, and AKT and to up-regulation of an IFN-gamma-related antiangiogenic pathway. Thus, IL-12R beta 2 directly restrains MM cell growth, and targeting of IL-12 to tumor cells holds promise as new therapeutic strategy.
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PMID:Constitutive expression of IL-12R beta 2 on human multiple myeloma cells delineates a novel therapeutic target. 1847 25

This study was purposed to investigate the immunophenotype characteristics in multiple myeloma (MM) cells and their significance. The expressions of CD138, CD38, CD56, CD117, HLA-DR, CD3, CD7, CD13, CD33, CD19, CD20, CD22, CD34 in myeloma cells from 31 MM patients were detected by using CD45/SSC immunofluorescent flow cytometry and were confirmed with morphologic observation of myeloma cells. The results indicated that the proportion of myeloma cells detected by morphologic examination was 10%-68%, the proportion of myeloma cells detected by CD45/SSC gating was 9.72%-67.77%. The antigen positive expression rate in myeloma cells was as follows: CD138 61.29%, CD38 100%, CD56 46.15%, CD13 70.00%, CD33 29.03%, HLA-DR 74.19%, CD117 33.33%; the other antigen expressions were negative. It is concluded that the use of CD45/SSC gating technique can identify multiple myeloma cells. The proportion of myeloma cells gated was close to the result of morphological examination. The myeloma cells mainly express the antigens CD138, CD88, CD56, while the expressions of CD117, CD13, CD33 were seen in some MM patients. Myeloma cells don't express antigens of B- and T-lymphocytes, which suggest the heterogenicity of multiple antigens expressed by myeloma cells. However, the biological significance of antigen expression in myeloma cells is worthy to be further investigated.
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PMID:[Immunophenotype characteristics in multiple myeloma cells and their significance]. 2041 73


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