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)

Recently, a new member of the gamma-herpesvirus family, human herpesvirus 8 (HHV-8), was identified in a case of Kaposi's sarcoma. This virus has also been found in the nonmalignant dendritic cells of the bone marrow from myeloma patients. In addition, HHV-8 is also detectable in the peripheral blood of most patients although its absence suggests earlier stage disease. By contrast, this virus is undetectable in the blood of family members and sexual partners of myeloma patients. Sequencing of HHV-8 open reading frames from myeloma patients show interpatient differences as well as consistent differences in the myeloma samples compared to HHV-8 in other malignancies associated with HHV-8 infection. Consistent expression of both the viral homologues of interferon regulatory factor and IL-8 receptor suggest a possible role for these transforming viral genes in the pathogenesis of myeloma. The latter gene is known to induce angiogenesis and preliminary studies show the abundance of vascular endothelial cells in the bone marrow of myeloma patients.
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PMID:HHV-8 and multiple myeloma. 1019 78

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.
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PMID:Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. 1020 Feb 99

The Kaposi's sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), has been found to be present in a limited subset of lymphoproliferative disorders. Among these are the primary effusion lymphomas, formerly designated body cavity-based lymphomas, a rare type of malignant lymphoma which possesses an unusual set of clinical and biologic features, suggesting that they represent a distinct disease entity. This virus is also present in a large proportion of cases of multicentric Castleman's disease, particularly those associated with HIV-infection. In addition, KSHV has been implicated in the pathogenesis of multiple myeloma, where it has been identified in bone marrow adherent cells but not in the neoplastic myeloma plasma cell population. However, the latter finding remains controversial. The discovery of KSHV in a subset of malignant lymphomas has allowed the development of lymphoma cell lines which now serve as biological reagents for propagating the virus, as a substrate for serologic assays, and as a model system for pathobiologic studies. This review discusses the features of KSHV-associated lymphoproliferative disorders and the evidence supporting its role in the pathogenesis of these diseases.
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PMID:The role of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in lymphoproliferative diseases. 1034 68

Following the demonstration in 1994, that Kaposi's sarcoma (KS) was associated with a novel virus (KSHV or HHV-8) belonging to the lymphotropic herpes family, this virus was also found in certain lymphoid neoplasias of immunodeficient (HIV+) and immune competent hosts. The association of HHV-8/KSHV infection is now well established with primary effusion lymphoma (PEL) or body cavity based lymphoma (BCBL) and multicentric Castleman's disease (MCD) of the plasma cell type. A possible pathogenic role of HHV-8/KSHV in other lymphoid tumours including primary central nervous system lymphoma (PCNSL) and multiple myeloma (MM) as well as some atypical lymphoproliferations and sarcoidosis has also been suggested, but this is at present a controversial matter, or not confirmed. Several HHV-8/KSHV genes, including potential oncogenes, genes homologous to various cellular genes and growth factors have been incriminated in the pathogenesis of KS and PEL/BCBL, but a common pathogenic mechanism for the clearly diverse proliferations represented by PEL, MCD and KS is at present not evident.
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PMID:Lymphoid disorders associated with HHV-8/KSHV infection: facts and contentions. 1038 36

Human herpes virus 8 (HHV-8) also known as Kaposi's sarcoma-associated herpes virus has been strongly implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. Recently, this gamma-herpes virus was also found in the nonmalignant bone marrow dendritic cells of the majority of myeloma patients. In addition, HHV-8 is also detectable in the peripheral blood of most myeloma patients. In contrast, this virus is rarely detected in close contacts of myeloma patients or healthy subjects. Furthermore, only about one-third of patients with monoclonal gammopathy of undetermined significance (MGUS) are infected with HHV-8. Sequencing of HHV-8 DNA isolated from myeloma patients shows both interpatient differences and conserved differences unique to myeloma compared to HHV-8 in other malignancies. Consistent expression of both the viral homologs of interferon regulatory factor and interleukin-8 receptor in myeloma suggests a possible role for these transforming viral genes in the pathogenesis of this disease.
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PMID:HHV-8 infection and multiple myeloma. 1044 81

Recently it was reported that Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) infects bone marrow (BM) dendritic cells (DC) in multiple myeloma (MM) patients and therefore might play a role in MM development. Because of the use of myeloid growth factors like GM-CSF and G-CSF for the mobilization of peripheral blood progenitor cells (PBPC), the subsequent increase of DC precursors might imply a risk for KSHV contamination in PBPC grafts. Therefore, in this study leukapheresis products and ex vivo cultured CD34+ cell suspensions were analysed. KSHV DNA could not be amplified in any of them.
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PMID:Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) DNA sequences are absent in leukapheresis products and ex vivo expanded CD34+ cells from multiple myeloma patients. 1088 29

IVIg is a preparation of normal polyspecific IgG obtained from pooled plasma of a large number of healthy donors. IVIg treatment of patients with chronic lymphocytic leukemia induced a reduction in the total number of lymphocytes in the peripheral blood. Regression of Kaposi's sarcoma was also noted in an HIV patient treated with IVIg. The aim of this study was to determine whether F(ab')2 prepared from IVIg binds to cellular structures of different tumor tissues. Biotinylated F(ab')2 was prepared from 3 different preparations of IVIg and from affinity purified IgG from a patient with multiple myeloma. Direct immunohistochemistry using a streptavidin peroxidase staining method was performed on biopsy samples of 18 different tumor tissues. Positive staining of the cytoplasm, cell membrane and nuclear membrane of several types of malignant tumors by F(ab')2 from IVIg was immunohistochemically demonstrated. Nuclear staining of tumor cells by IVIg was rare. IVIg bound to different tumors of epithelial origin, especially colon carcinoma, breast carcinoma and squamous cell carcinoma of the lung. Malignant tumors of mesenchymal origin such as leiomyosarcoma have also demonstrated positive staining by IVIg. IVIg contains antibodies to the cytoplasm, nuclear membrane and cell membrane of different malignant tumors especially of epithelial origin. This binding might provide a basis for the assumption that IVIg treatment of cancer patients may induce antibody dependent cell mediated cytotoxicity response against tumors, and implies that it can be potentially beneficial as adjuvant treatment of malignant diseases.
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PMID:Antibodies to the cytoplasm, cell membrane and nuclear membrane of malignant neoplasms in pooled normal human polyspecific immunoglobulin G. 1056 13

Human herpesvirus 8 is a novel gamma-herpesvirus that has been linked with all clinical types of KS through both DNA and serologic studies. By electron microscopic, in situ hybridization, and in situ PCR studies, virus is found in tumor spindle cells, in normal-appearing endothelial cells within lesions, and in tumor-infiltrating leukocytes. The fact that most tumor cells are latently, as opposed to lytically, infected with HHV8 makes the possibility of treating KS patients with antiherpesviral medications unlikely. Human herpesvirus 8 infection is also associated with BCBL and CD and has recently been reported in patients with multiple myeloma and sarcoidosis (although these latter associations have not been substantiated). Interestingly, the HHV8 genome contains many genes that could be involved in evading normal immune surveillance. Importantly, B-cell lines derived from patients with BCBL have been extremely useful in elucidating the virologic and biological properties of HHV8. In summary, both HHV8 gene analyses and clinico-epidemiologic studies generated by many research teams throughout the world support the concept that HHV8 is the etiologic agent of KS. Future research will focus on developing in vitro model systems to study KS, delineating the expression pattern and function of HHV8-encoded proteins in vivo, determining factors that lead to the development of KS in HHV8-infected individuals, and devising novel therapeutic strategies for KS based on these advances in basic science.
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PMID:The role of human herpesvirus 8 in the pathogenesis of Kaposi's sarcoma. 1064 99

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), has recently been identified within the bone marrow dendritic cells of multiple myeloma (MM) patients. This virus contains homologues to human cytokines such as IL-6 that could potentially stimulate myeloma cell growth and contribute to disease pathogenesis. Since mobilization chemotherapy may increase circulating dendritic cell numbers, we searched for HHV-8 in peripheral blood mononuclear cells (PBMCs) before and after mobilization chemotherapy given to MM patients. Furthermore, we determined if autograft purging using the CEPRATE SC device would reduce the percentage of HHV-8 infected stem cell products. Only two of the 39 PBMC samples collected prior to mobilization chemotherapy contained PCR detectable virus, yet nine of 37 PBMCs collected on the first day of leukapheresis had detectable HHV-8 (P = 0.016). HHV-8 was more frequently identified in autograft products before vs after Ceprate SC selection (40% vs 15%, P = 0.016). Although the role HHV-8 plays in myeloma pathogenesis remains unclear, these results imply that mobilization chemotherapy increases the numbers of circulating HHV-8-infected dendritic cells within the peripheral blood. In addition, CD34 selection of autograft products in MM patients may reduce the reintroduction of virally infected cells following high-dose chemotherapy. Bone Marrow Transplantation (2000) 25, 153-160.
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PMID:Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients. 1067 73

The causes of multiple myeloma (MM) are obscure, but a laboratory association was recently reported between MM and human herpesvirus 8 (HHV-8), the probable etiologic agent of Kaposi's sarcoma (KS). Although there has been some additional laboratory corroboration, most laboratory studies have found no association between MM and HHV-8. We looked for indirect evidence of an HHV-8/MM association by evaluating whether MM is associated with KS in the United States. Cancer incidence and survival data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program for the years 1973-1995. Strength of association was assessed for a number of cancer pairs using standardized incidence ratios (SIRs) (observed/expected double cancers). KS was strongly associated (SIR > 15) with non-Hodgkin's lymphoma and anal cancer, was modestly associated (2.5 < SIR < 5.5) with MM, Hodgkin's disease, and testicular cancer and was not significantly associated with 6 other cancers. Besides being associated with KS, MM was weakly associated (1.7 < SIR < 2.3) with Hodgkin's disease and testicular cancer. The SIRs for 7 other cancers paired with MM were all less than 1.6. Factors that might be responsible for the KS/MM association include MM-related immune dysfunction, HIV and HHV-8, but the role of these factors cannot be directly assessed through the SEER database. Although we cannot rule out the possibility that HHV-8 is linked to a small proportion of MM cases, the modest KS/MM association is evidence that the vast majority of MM cases are not likely to be associated with HHV-8.
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PMID:Occurrence of primary cancers in association with multiple myeloma and Kaposi's sarcoma in the United States, 1973-1995. 1069 13


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