scholarly journals Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 498-504 ◽  
Author(s):  
D Emilie ◽  
J Coumbaras ◽  
M Raphael ◽  
O Devergne ◽  
HJ Delecluse ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Interleukin 6 ◽  
Large Cell ◽  
Malignant Cell ◽  
High Grade ◽  
Follicular Hyperplasia ◽  
Immunodeficiency Virus ◽  
Hodgkin's Lymphomas

The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large- cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.

scholarly journals Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 498-504 ◽  
Author(s):  
D Emilie ◽  
J Coumbaras ◽  
M Raphael ◽  
O Devergne ◽  
HJ Delecluse ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Interleukin 6 ◽  
Large Cell ◽  
Malignant Cell ◽  
High Grade ◽  
Follicular Hyperplasia ◽  
Immunodeficiency Virus ◽  
Hodgkin's Lymphomas

Abstract The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large- cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.

Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.

1990 ◽  
Vol 8 (1) ◽  
pp. 94-102 ◽  
Author(s):  
A M Schneider ◽  
D J Straus ◽  
A E Schluger ◽  
D A Lowenthal ◽  
B Koziner ◽  
...  
Keyword(s):  
Performance Status ◽  
Large Cell ◽  
Hiv Positive ◽  
High Grade ◽  
Bulky Disease ◽  
Chemotherapeutic Regimen ◽  
Immunodeficiency Virus ◽  
Wbc Count ◽  
Hodgkin's Lymphomas

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.

Human immunodeficiency virus-associated systemic lymphomas may be subdivided into two main groups according to Epstein-Barr viral latent gene expression.

1993 ◽  
Vol 11 (9) ◽  
pp. 1674-1681 ◽  
Author(s):  
A Carbone ◽  
U Tirelli ◽  
A Gloghini ◽  
R Volpe ◽  
M Boiocchi
Keyword(s):  
Gene Expression ◽  
Human Immunodeficiency Virus ◽  
B Cell ◽  
Cell Morphology ◽  
Large Cell ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Epstein Barr

PURPOSE We report a pathologic characterization of human immunodeficiency virus (HIV)-associated systemic lymphomas, including the association of Epstein-Barr virus (EBV) in different categories. PATIENTS AND METHODS Eighty-seven HIV-associated non-Hodgkin's lymphoma (NHL) were classified according to classic NHL classification and a recent description of morphologic variants of high-grade B-cell NHL. Seventy-one cases were immunophenotypically-genotypically characterized, whereas, in 49 representative cases, the association of EBV was assessed by nonisotopic in situ hybridization (ISH) and the immunohistochemical demonstration of latent membrane protein-1 (LMP-1). In addition, 14 Hodgkin's disease (HD) cases, occurring in patients with HIV infection, were investigated for the frequency of LMP-1 expression. RESULTS Most lymphomas were of B-cell derivation and showed a blastic cell morphology, with (1) small noncleaved cells (SNCCs; 36 cases), (2) large noncleaved cells (10 cases), and (3) immunoblasts, usually polymorphic (12 cases). Moreover, 12 cases were classified as anaplastic large-cell (ALC) Ki-1-positive (Ki-1+) lymphoma. Combined ISH studies (for viral DNA and EBV RNA [EBER]) and immunohistologic demonstration of LMP-1 suggested that there were differences in viral latent gene expression between ALC Ki-1+ or immunoblastic lymphomas (usually EBV+, LMP-1+), and EBV-infected cells of SNCC lymphomas, which did not show LMP-1 expression. A high proportion (10 of 14) of LMP-1+ HD cases was found. CONCLUSION Differences in EBV association and LMP-1 expression were found between a major group of HIV-associated systemic NHL with blastic cell morphology, including SNCC lymphoma and its variants, and anaplastic cell lymphomas. A proportion of immunoblastic (polymorphic) lymphomas was different in viral latent gene expression from other blastic cell systemic lymphomas. It is concluded that only a group of these lymphomas (most ALC Ki-1+ and HD cases, along with a nonnegligible fraction of immunoblastic lymphomas) seems to be linked etiopathologically to EBV.

Burkitt-like lymphomas in AIDS patients: characterization within a series of 103 human immunodeficiency virus-associated non-Hodgkin's lymphomas. Burkitt's Lymphoma Study Group.

1998 ◽  
Vol 16 (12) ◽  
pp. 3788-3795 ◽  
Author(s):  
F Davi ◽  
H J Delecluse ◽  
P Guiet ◽  
J Gabarre ◽  
A Fayon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Large Cell ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Myc Oncogene ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr ◽  
Lymphoma Study Group ◽  
Hodgkin's Lymphomas

PURPOSE Burkitt-like lymphoma (BLL) is a tumor with morphologic features intermediate between Burkitt's lymphoma (BL) and large-cell lymphoma, but its relationship with these lymphomas is currently unclear. We have therefore analyzed its characteristics within a large series of human immunodeficiency virus (HIV)-associated lymphomas. MATERIALS AND METHODS Clinical, histologic, immunophenotypic, and molecular analyses were performed on 103 patients with AIDS lymphomas. RESULTS Nineteen cases (18.4%) were identified as BLL. They were monoclonal B-cell proliferations, as evaluated by immunoglobulin (Ig) gene rearrangement analyses, and had rearrangement of the c-myc oncogene in 68% of cases but not the bcl-2 gene, in contrast to a previous study on non-HIV-associated BLL. This molecular pattern was therefore identical to that of typical BL, suggesting that they represented tumors of similar origin. However, some features could clearly differentiate BLL from BL and were similar to those seen in the diffuse large-cell immunoblastic lymphomas (DLC-IBL) group. These included a greater frequency of Epstein-Barr Virus (EBV) infection (79% v 48%, P = .04), an upregulation of CD39 (50% v 0%, P = .0007) and CD70 (75% v 15%, P = .003) activation antigens and of the CD11a/LFA-1 adhesion molecule (83% v30%, P = .05), and, finally, a lower CD4 count (mean, 119/microL v 270/microL, P = .04). CONCLUSION BLL is a frequent entity among AIDS lymphomas and should be considered as a morphologic variant of BL in the context of severe immunodepression that occurs in HIV-infected patients.

Extensive Enteric Leiomyolysis Due to Cytomegalovirus Enterocolitis in Vertically Acquired Human Immunodeficiency Virus Infection in Infants

2000 ◽  
Vol 3 (6) ◽  
pp. 591-596 ◽  
Author(s):  
Virpi V. Smith ◽  
Amanda J. Williams ◽  
Vas Novelli ◽  
Marian Malone
Keyword(s):  
Human Immunodeficiency Virus ◽  
Vascular Endothelium ◽  
Muscularis Propria ◽  
The Other ◽  
Muscularis Mucosae ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Viral Inclusions

We report two infants with the acquired immunodeficiency syndrome (AIDS) and rectal bleeding due to cytomegalovirus (CMV) ileitis and colitis with minimal focal mucosal ulceration but with extensive leiomyolysis of the muscularis propria. Immunostaining and in situ hybridization for CMV showed numerous viral inclusions in the myocytes of the muscularis propria and vascular endothelium/smooth muscle with only occasional inclusions present in the muscularis mucosae. Colectomy was curative in one patient; in the other the bowel was only examined at postmortem.

scholarly journals Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

1991 ◽  
Vol 173 (3) ◽  
pp. 589-597 ◽  
Author(s):  
G Poli ◽  
A L Kinter ◽  
J S Justement ◽  
P Bressler ◽  
J H Kehrl ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Immunodeficiency Virus ◽  
Growth Factor Beta

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

Evidence for Involvement of Transforming Growth Factor β1 Signaling Pathway in Activation of JC Virus in Human Immunodeficiency Virus 1–Associated Progressive Multifocal Leukoencephalopathy

2004 ◽  
Vol 128 (3) ◽  
pp. 282-291
Author(s):  
Sahnila Enam ◽  
Thersa M. Sweet ◽  
Shohreh Amini ◽  
Kamel Khalili ◽  
Luis Del Valle
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Transforming Growth Factor ◽  
Jc Virus ◽  
Transforming Growth Factor Β1 ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Human Immunodeficiency Virus 1

Abstract Context.—Progressive multifocal leukoencephalopathy is a fatal demyelinating disease of the central nervous system frequently seen in patients with impaired immune systems, particularly acquired immunodeficiency syndrome. JC virus (JCV), a human neurotropic polyomavirus, is the etiologic infectious agent of this disease. Objective.—The significantly higher incidence of progressive multifocal leukoencephalopathy in patients with acquired immunodeficiency syndrome than in patients with other immunosuppressive conditions suggests that molecular interactions between human immunodeficiency virus 1 and JCV, via the Tat protein, are responsible for the activation of the JCV enhancer/promoter and the development of progressive multifocal leukoencephalopathy. An indirect mechanism through activation of cytokines, such as transforming growth factor β1 and Smads 3 and 4, may also be responsible for the enhancement of JCV gene expression. Design.—Immunohistochemical analysis in progressive multifocal leukoencephalopathy samples and chloramphenicol acetyl transferase assays on cell cultures were performed to corroborate this hypothesis. Results.—The JCV capsid protein VP-1 was found in the nuclei of oligodendrocytes and in the nuclei and cytoplasm of bizarre astrocytes. Human immunodeficiency virus proteins, including p24 and Tat, were detected in the cytoplasm of astrocytes. Tat, but not p24, was detected in oligodendrocytes, suggesting that extracellular Tat accumulates in the nuclei of oligodendrocytes, where JCV gene transcription takes place. High levels of transforming growth factor β1 and Smads 3 and 4 were detected in JCV-infected oligodendrocytes. Results from in vitro studies confirm activation of the JCV early and late promoters by Smads 3 and 4. Conclusions.—These observations support our model, suggesting that the induction of transforming growth factor β1 by human immunodeficiency virus 1 Tat can stimulate its downstream factors, including Smads 3 and 4, which in turn augment transcription of the JCV promoter in glial cells.

Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus–related lymphomas

Blood ◽  
2001 ◽  
Vol 97 (3) ◽  
pp. 744-751 ◽  
Author(s):  
Antonino Carbone ◽  
Annunziata Gloghini ◽  
Luigi M. Larocca ◽  
Daniela Capello ◽  
Francesco Pierconti ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
B Cells ◽  
B Cell ◽  
Primary Effusion Lymphoma ◽  
Large Fraction ◽  
Large Cell ◽  
Barr Virus ◽  
Immunoblastic Lymphoma ◽  
Immunodeficiency Virus ◽  
Epstein Barr

Abstract This study was aimed at defining the histogenesis of the pathologic spectrum of lymphoma arising in the context of human immunodeficiency virus (HIV) infection. Toward this aim, 87 AIDS-related non-Hodgkin lymphomas (AIDS-NHL) and 16 Hodgkin lymphomas arising in HIV+ patients (HIV-HL) were comparatively analyzed for the expression pattern of several B-cell histogenetic markers, including BCL-6 (expressed by centroblasts and centrocytes), MUM1/IRF4 (expressed by late centrocytes and post–germinal center [GC] B cells), and CD138/syn-1 (expressed by post-GC B cells). Expression of MUM1, BCL-6, and syn-1 segregated 3 major phenotypic patterns among AIDS-NHL and HIV-HL: (1) the BCL-6+/MUM1−/syn-1− pattern, selectively clustering with a large fraction of AIDS-Burkitt lymphoma (17 of 19) and of systemic AIDS–diffuse large cell lymphoma (12 of 16); (2) the BCL-6−/MUM1+/syn-1−pattern, associated with a fraction of AIDS-immunoblastic lymphoma (8 of 24); and (3) the BCL-6−/MUM1+/syn-1+ pattern, associated with systemic and primary central nervous system immunoblastic lymphoma (14 of 24) and with primary effusion lymphoma (10 of 10), plasmablastic lymphoma of the oral cavity (7 of 7), and HIV-HL (15 of 16). Analysis of nonneoplastic lymph nodes showed that the 3 phenotypic patterns detected in AIDS-NHL and HIV-HL correspond to distinct stages of physiologic B-cell development—centroblasts (BCL-6+/MUM1−/syn-1−), late GC/early post-GC B cells (BCL-6−/MUM1+/syn-1−), and post-GC B cells (BCL-6−/MUM1+/syn-1+). Expression of the Epstein-Barr virus-encoded latent membrane protein-1 clustered with the BCL-6−/MUM1+/syn-1+profile throughout the clinicopathologic spectrum of AIDS-NHL and HIV-HL. Overall, these results define novel histogenetic subsets of AIDS-NHL and HIV-HL and may provide novel tools for refining the diagnosis of these disorders.

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