Blood Dendritic Cells From Myeloma Patients Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8)

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 402-404 ◽  
Author(s):  
Qing Yi ◽  
Marianne Ekman ◽  
Doina Anton ◽  
Susanne Bergenbrant ◽  
Anders Österborg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Herpes Virus ◽  
Bone Marrow Cells ◽  
Kaposi’S Sarcoma ◽  
Myeloma Cell ◽  
Herpès Virus ◽  
Marrow Cells

In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of patients with multiple myeloma (MM). A concern was raised whether there is an causal association between the viral infection and development of these tumors. In the present study, we have examined DC generated from blood adherent cells from 8 Swedish MM patients at different clinical stages and 2 patients with monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell lines and bone marrow cells from 2 MM patients were also studied. By polymerase chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no antibody against KSHV was found in the serum of these 10 patients. Thus, our results indicate that blood-derived DC of MM patients in Sweden usually are not infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not regularly associated with MM and consequently does not play a primary role in the pathogenesis of these tumors.

Blood Dendritic Cells From Myeloma Patients Are Not Infected With Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8)

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 402-404 ◽  
Author(s):  
Qing Yi ◽  
Marianne Ekman ◽  
Doina Anton ◽  
Susanne Bergenbrant ◽  
Anders Österborg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Cell Lines ◽  
Kaposi's Sarcoma ◽  
Herpes Virus ◽  
Bone Marrow Cells ◽  
Kaposi’S Sarcoma ◽  
Myeloma Cell ◽  
Herpès Virus ◽  
Marrow Cells

Abstract In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of patients with multiple myeloma (MM). A concern was raised whether there is an causal association between the viral infection and development of these tumors. In the present study, we have examined DC generated from blood adherent cells from 8 Swedish MM patients at different clinical stages and 2 patients with monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell lines and bone marrow cells from 2 MM patients were also studied. By polymerase chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no antibody against KSHV was found in the serum of these 10 patients. Thus, our results indicate that blood-derived DC of MM patients in Sweden usually are not infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not regularly associated with MM and consequently does not play a primary role in the pathogenesis of these tumors.

scholarly journals Mechanisms of Growth Control of Kaposi's Sarcoma–Associated Herpes Virus–Associated Primary Effusion Lymphoma Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2475-2481 ◽  
Author(s):  
Hiroya Asou ◽  
Jonathan W. Said ◽  
Rong Yang ◽  
Reinhold Munker ◽  
Dorothy J. Park ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Antisense Oligonucleotides ◽  
Clonal Growth ◽  
Kaposi's Sarcoma ◽  
Herpes Virus ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Gm Csf ◽  
Herpès Virus

Abstract Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with Kaposi's sarcoma-associated herpes virus (KSHV). Several cytokines, including interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) may be important for survival of KS cells. However, little is known about the interaction of cytokines with KSHV-infected lymphocytes from PEL. Therefore, we investigated what cytokines were produced by KSHV-infected PEL cell lines (KS-1, BC-1, BC-2), what cytokine receptors were expressed by these cells, what response these cells had to selected cytokines, and what was the effect of IL-6 antisense phosphorothioated oligonucleotides. Reverse transcriptase-polymerase chain reaction (RT-PCR) and protein studies showed that these three cell lines produced IL-10, IL-6, and the receptors for IL-6. The granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-8, IL-12, bFGF, PDGF, and c-kit transcripts were not detected in the cell lines. High levels (0.7 to 5 ng/mL/106cells/48 hours) of IL-6 protein were consistently detected in supernatants of the cell lines by enzyme-linked immunosorbent assay (ELISA) tests. In clonogenic assays, interferon-α (IFN-α) and IFN-γ suppressed the clonal growth of the PEL cells, but GM-CSF, IL-4, IL-6, IL-8, IL-10, and oncostatin M did not change it. We examined for several autocrine loops that have been suggested to occur in KS. Experiments using antisense oligonucleotides showed that the clonal growth of KS-1 and BC-1 was nearly 100% inhibited by IL-6 antisense oligonucleotides (10 μmol/L), but not at all by either oligonucleotides (≤10 μmol/L) to IL-6 sense, IL-6 scrambled, viral IL-6 (vIL-6) antisense, or IL-10 antisense. Furthermore, the IL-6 antisense oligonucleotides had no effect on two B-cell lymphoma cell lines, which were not infected with KSHV. Addition of IL-6 antibody did not inhibit clonal growth of any of the cell lines. Taken together, we have defined the cytokines and their receptors expressed on PEL cells and have found that these cells synthesized IL-6 and IL-6 receptors; interruption of this pathway by IL-6 antisense oligonucleotides specifically prevented the growth of these cells. These findings will offer potential new therapeutic strategies for PEL.

Silencing Immunoglobulin Gene Enhancers as a Potential Treatment Strategy for Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5162-5162
Author(s):  
Inka Toman ◽  
Jonathan Loree ◽  
Kim Duerksen ◽  
Robert Evans ◽  
Tony Reiman
Keyword(s):  
Bone Marrow ◽  
Cell Viability ◽  
Cell Lines ◽  
Plasma Cell ◽  
Treatment Strategy ◽  
Bone Marrow Cells ◽  
Myeloma Cell ◽  
Immunoglobulin Gene ◽  
Potential Treatment ◽  
Marrow Cells

Abstract Background: Primary translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14q32 occur in 60–75% of myeloma cases. This results in oncogenes from translocated chromosomes being overexpressed by linkage to the strong IgH enhancers. Specifically inhibiting the activity of a single translocated oncogene product (e.g. FGFR3 in t(4;14)+ myeloma) has been shown to decrease proliferation and increase apoptosis only in myeloma cells harboring the relevant translocation. Several recurrent translocations have been identified in myeloma, and in many cases the partner loci are non-recurrent or unidentified. No single translocation partner has been found in more than 15–20% of myelomas, and more than one overexpressed gene on the partner locus can be pathogenic (e.g. FGFR3 and MMSET). This limits the widespread applicability and potential effectiveness of therapies that directly target only one IgH-translocated oncogene. We hypothesize that silencing the IgH enhancers is a potential treatment strategy for all IgH translocation-positive myelomas, regardless of the oncogenes involved in the translocation. We further hypothesize that by specifically targeting the B/plasma cell specific transcription factors Oct-2 and Bob-1 that partially drive the IgH enhancer, a therapy could be designed with minimal toxicity to normal tissues apart from B-lineage cells. Methods: Expression of Oct-2 and Bob-1 genes and proteins were assayed with qRT-PCR and Western blot in 6 myeloma cell lines harbouring different (or no) IgH translocations, in AutoMACS-purified CD138+ and CD138− bone marrow cells from 36 patients, and in bone marrow core biopsies from 30 patients with immunohistochemistry. Using RNA interference (RNAi), we inhibited the expression of Bob-1 in KMS-11, a myeloma cell line that overexpresses fibroblast growth factor receptor 3 (FGFR3) due to a t(4;14) translocation. The effects of Bob-1 RNAi on FGFR3 expression, cell viability and induction of apoptosis were assayed by MTS and Annexin V/propidium iodide flow cytometry assays respectively. Results: Oct-2 and Bob-1 are ubiquitously expressed in myeloma cell lines and patient plasma cells, irrespective of translocation status. Both mRNA and protein expression are much greater in CD138+ myeloma bone marrow cells than in CD138− cells, and vary among patients. We will present updated results on a larger patient cohort at the meeting, along with clinical correlations including the prognostic significance of Oct-2 and Bob-1 expression levels. In keeping with decreased activity of the IgH enhancer, a decrease in the level of FGFR3 protein was observed following Bob-1 RNAi knockdown in KMS-11. Furthermore, Bob-1 knockdown led to a reduction in cell viability, and an increase in apoptosis. Discussion: Overall, these results demonstrate the potential of Bob-1 and possibly Oct-2 as therapeutic targets for the treatment of translocation-positive myeloma, due to both their contribution to overexpression of translocated oncogenes, as well as their selective and high expression in the plasma cell population. Clinically applicable approaches to Bob-1 or Oct-2 inhibition are under consideration in our laboratory.

Over Expression of YY1 and RKIP in Multiple Myeloma (Cell Lines and MM Tissues).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5035-5035
Author(s):  
Stavroula Baritaki ◽  
Sara Huerta-Yepez ◽  
Alina Katsman ◽  
Kam C. Yeung ◽  
Devasis Chatterjee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Myeloma Cell ◽  
Gene Products ◽  
Normal Bone Marrow ◽  
Over Expression ◽  
Normal Bone ◽  
Marrow Cells

Abstract There is a need to identify underlying molecular mechanisms and gene products (targets for intervention and biomarkers) involved in MM chemo- or immuno-resistance. Recent findings from our laboratory have reported high expression of the transcription factor Yin Yang 1 (YY1) in several tumor types and have demonstrated its fundamental role in tumor cell chemo/immuno-resistance (Gordon, S., et al., Oncogene25:1125, 2006). In contrast, low levels of the Raf kinase inhibitor protein (RKIP) has been shown to play a pivotal role in the negative regulation of cell survival signaling pathways, and has been considered a metastasis tumor suppressor. The overall objective of our studies is to examine whether MM cell lines and tissues derived from MM patients present deregulated expression patterns of RKIP and YY1, and to demonstrate the roles of YY1 and RKIP in MM pathogenesis and response to various therapies. In the present study, the myeloma cell lines RPMI-8226 and MM-1S were screened for RKIP and YY1 expression at the protein and m-RNA levels. In addition, fresh tissues from MM patients were also examined for RKIP and YY1 expression by IHC and their patterns compared with those observed in normal bone marrow cells. The findings demonstrate that both MM cell lines express remarkably higher levels of RKIP protein and transcripts compared to other tumor cell lines examined (lymphomas and prostate cancer), as assessed by western, RT-PCR and IHC. There was significantly higher expression of RKIP in MM patient’s samples compared to normal bone marrow cells. YY1 protein and m-RNA levels were detected in the MM cell lines; however, they were lower compared to Ramos and PC-3 cells. YY1 expression in MM tissues was significantly elevated compared to normal bone marrow cells. RKIP was basically present in the cytoplasm while YY1 was mainly accumulated in the nucleus. In contrast, normal bone marrow cells presented primarily cytoplasmic YY1 and RKIP expression. The YY1 expressing population was the CD38+/CD138− cell subset, which has been reported to be more susceptible to apoptosis (Mitsiadis, S.C., et al., Blood 98:795, 2001). Overall, the present findings support the potential involvement of two new gene products, such as YY1 and RKIP, in MM pathogenesis and their implication in regulating MM resistance to conventional therapeutics. Moreover, these gene products suggest their potential use as new therapeutic targets and/or biomarkers in multiple myeloma. Future studies with large cohorts of tissues will elucidate the importance of the above findings and will give new insights in the unexpected RKIP over expression and activity in multiple myeloma.

scholarly journals Mechanisms of Growth Control of Kaposi's Sarcoma–Associated Herpes Virus–Associated Primary Effusion Lymphoma Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2475-2481 ◽  
Author(s):  
Hiroya Asou ◽  
Jonathan W. Said ◽  
Rong Yang ◽  
Reinhold Munker ◽  
Dorothy J. Park ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Antisense Oligonucleotides ◽  
Clonal Growth ◽  
Kaposi's Sarcoma ◽  
Herpes Virus ◽  
Primary Effusion Lymphoma ◽  
Kaposi’S Sarcoma ◽  
Gm Csf ◽  
Herpès Virus

Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with Kaposi's sarcoma-associated herpes virus (KSHV). Several cytokines, including interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) may be important for survival of KS cells. However, little is known about the interaction of cytokines with KSHV-infected lymphocytes from PEL. Therefore, we investigated what cytokines were produced by KSHV-infected PEL cell lines (KS-1, BC-1, BC-2), what cytokine receptors were expressed by these cells, what response these cells had to selected cytokines, and what was the effect of IL-6 antisense phosphorothioated oligonucleotides. Reverse transcriptase-polymerase chain reaction (RT-PCR) and protein studies showed that these three cell lines produced IL-10, IL-6, and the receptors for IL-6. The granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-8, IL-12, bFGF, PDGF, and c-kit transcripts were not detected in the cell lines. High levels (0.7 to 5 ng/mL/106cells/48 hours) of IL-6 protein were consistently detected in supernatants of the cell lines by enzyme-linked immunosorbent assay (ELISA) tests. In clonogenic assays, interferon-α (IFN-α) and IFN-γ suppressed the clonal growth of the PEL cells, but GM-CSF, IL-4, IL-6, IL-8, IL-10, and oncostatin M did not change it. We examined for several autocrine loops that have been suggested to occur in KS. Experiments using antisense oligonucleotides showed that the clonal growth of KS-1 and BC-1 was nearly 100% inhibited by IL-6 antisense oligonucleotides (10 μmol/L), but not at all by either oligonucleotides (≤10 μmol/L) to IL-6 sense, IL-6 scrambled, viral IL-6 (vIL-6) antisense, or IL-10 antisense. Furthermore, the IL-6 antisense oligonucleotides had no effect on two B-cell lymphoma cell lines, which were not infected with KSHV. Addition of IL-6 antibody did not inhibit clonal growth of any of the cell lines. Taken together, we have defined the cytokines and their receptors expressed on PEL cells and have found that these cells synthesized IL-6 and IL-6 receptors; interruption of this pathway by IL-6 antisense oligonucleotides specifically prevented the growth of these cells. These findings will offer potential new therapeutic strategies for PEL.

MOLECULAR DETECTION OF KAPOSI’S SARCOMA ASSOCIATED VIRUS (HUMAN HERPES VIRUS 8) IN SINO-NASAL CARCINOMA TISSUES

2020 ◽  
Vol 23 (04) ◽  
pp. 286-297
Author(s):  
Hind Hamed Shaker ◽  
Luma Amer Yasir ◽  
Ausama Abed-Alkadum Alajeely ◽  
Saad Hasan Mohammed Ali ◽  
Shakir H. Mohammed Al-Alwany
Keyword(s):  
Kaposi's Sarcoma ◽  
Herpes Virus ◽  
Molecular Detection ◽  
Kaposi’S Sarcoma ◽  
Human Herpes ◽  
Human Herpes Virus 8 ◽  
Human Herpes Virus ◽  
Herpès Virus ◽  
Nasal Carcinoma

Targeting the PI3K and MAPK pathways to treat Kaposi’s sarcoma-associated herpes virus infection and pathogenesis

2007 ◽  
Vol 11 (5) ◽  
pp. 589-599 ◽  
Author(s):  
Phelps J Lambert ◽  
Aniqa Z Shahrier ◽  
Audy G Whitman ◽  
Ossie F Dyson ◽  
Adrian J Reber ◽  
...  
Keyword(s):  
Virus Infection ◽  
Kaposi's Sarcoma ◽  
Herpes Virus ◽  
Kaposi’S Sarcoma ◽  
Herpes Virus Infection ◽  
Mapk Pathways ◽  
Herpès Virus
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