HIV: implication in Burkitt lymphoma (original) (raw)
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Analysis of stepwise genetic changes in an AIDS-related Burkitt's lymphoma
International Journal of Cancer, 2000
In this study, immunoglobulin variable (Ig V) region genes, c-myc re-arrangement and sequence and p53 status were analyzed in clones derived from a Burkitt's lymphoma cell line (LAM) in which it was previously demonstrated that Epstein-Barr virus (EBV) infection occurred late during lymphomagenesis. Such evidence was based on the finding that 2 groups of cellular clones, characterized by the same c-myc re-arrangement but different EBV-fused termini, were obtained from the LAM cell line. The Ig V gene sequences were identical for the 2 groups of clones with different EBV-fused termini. The Ig variable heavy (V H ) gene sequence displayed a substantial accumulation of point mutations (but no intraclonal diversification), whereas the productive Ig V lambda (V ) gene sequence was virtually unmutated. Studies on the Ig V kappa (V ) locus suggested a receptor revision event (with a switch from to chain production) prior to EBV infection. Likewise, it was determined that the mutations observed in both p53 alleles and in the re-arranged c-myc gene occurred before EBV infection. Based on these findings, we present a model for the various steps of lymphomagenesis. It is proposed that stimulation by an antigen or a superantigen initially favored the clonal expansion and accumulation of other cytogenetic changes, including those involved in receptor editing. These events occurred prior to or during the germinal center (GC) phase of B-cell maturation. Thereafter, possibly upon exit of the cells from the GC, EBV infection occurred, further promoting lymphomagenesis. Int.
American Journal of Clinical Pathology, 2005
Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.
Biological B-cell stimulatory biomarkers in HIV-associated non-hodgkin lymphoma
2016
Background: Human Immunodeficiency Virus (HIV) is an epidemic in South Africa with a rise in AIDS-defining malignancies, particularly Non-Hodgkin Lymphoma (NHL). B-cell stimulatory markers have been implicated in the risk and development of HIV-associated NHL. The mechanisms of the pathogenesis of HIV-associated NHL have not been fully elucidated but include: B-cell hyperactivation mediated by the over production of cytokines as a consequence of reduced immunosurveillance associated with CD4+ T-cell deficiencies. AIM: This study aimed to investigate and quantify the expression of B-cell stimulatory biomarkers in plasma and determine their contribution to lymphomagenesis in an HIV positive South African cohort. Methods: Plasma samples from HIV positive patients with confirmed NHL and HIV positive patients without evidence of lymphoma were assessed for ten cytokines: Interleukin (IL) IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony stimulating factor (GM-CSF), interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα), as well as two soluble factors, sCD23 and sCD30 by Luminex Technology and ELISA respectively. Peripheral blood mononuclear cells from a HIV positive patient with Burkitts lymphoma were used to establish an in vitro culture. Results: Cytokines IL-6, IL-8 and IL-10 concentrations (pg/ml) were significantly elevated in HIV positive patients with NHL compared to the HIV positive controls. Soluble factors CD23 and CD30 concentrations (U/ml) were also elevated in HIV positive patients with NHL. Conclusion: IL-6, IL-8 and IL-10 may play a key role in stimulating B-cell proliferation and lymphomagenesis. IL-6 and IL-8 are pleiotropic pro-inflammatory cytokines, and IL-10 an anti-inflammatory and/or regulatory cytokine, that act as growth factors in a paracrine or autocrine manner for HIV-associated lymphoma cells.
B cell lymphoma in hiv transgenic mice
Retrovirology, 2013
Background: Human Immunodeficiency Virus Type I (HIV-1) infection is associated with a high incidence of B-cell lymphomas. The role of HIV in these lymphomas is unclear and currently there are no valid in vivo models for better understanding HIV-related lymphomagenesis. Transgenic (Tg) 26 mice have a 7.4-kb pNL4-3 HIV-1 provirus lacking a 3.1-kb sequence encompassing parts of the gag-pol region. Approximately 15% of these HIV Tg mice spontaneously develop lymphoma with hallmark pre-diagnostic markers including skin lesions, diffuse lymphadenopathy and an increase in pro-inflammatory serum cytokines. Here we describe the phenotypic and molecular characteristics of the B cell leukemia/lymphoma in the Tg mice.
Burkitt's lymphoma Associated with HIV Infection
Non-Hodgkin lymphoma of the B-cell type is the second most common neoplasm in patients with human immunodeficiency virus infection after Kaposi's sarcoma. The majority of the cases of non-Hodgkin lymphoma associated with the acquired immunodeficiency syndrome involve extranodal sites, specially the digestive tract, including the oral cavity and the central nervous system. The estimated relative risk of NHL associated HIV infection is 100 times greater than in general population and this risk increases with the progressive immunosuppression related to the retrovirus Burkitt's lymphoma has frequently been reported as a neoplasm in HIV infected patients. These lymphomas are now better designed as AIDS-related BL.
International Journal of Cancer, 1990
Six AIDS-related NHLs from direct blood-stream HIVinfected patients were characterized for clonality, maturation cell characteristics, activation of c-myc proto-oncogene and presence of HIV and EBV genomes. Four out of the 6 AIDSrelated NHLs were of immature 6-cell origin, contrasting with the lower frequency (2 out of 31) of immature B-cell NHLs occurring in HIV-negative patients. Moreover, 3 out of the 4 AIDS-related pre-B-NHLs were extranodal lymphomas. C-myc translocations or rearrangements were not found in Italian AIDS-related NHLs, unlike c-myc activation which had a high prevalence in the American series of AIDS-related NHb. HIV and EBV are not, or only occasionally, directly involved in AIDS-related NHL pathogenesis since HIV genome has never been found in the neoplastic clones and EBV genome was detected in only I out of the 6 lymphomas analyzed.
Mediterranean Journal of Hematology and Infectious Diseases, 2009
HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV of HIV-associated lymphoma is significantly higher c population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART) (1). Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B Burkitt lymphoma (BL), Hodgkin primary central nervous system lymphoma (PCNSL), nasopharyngeal carcinoma (NC). Virus-associated lymphomas are becoming of significant concern for the mortality of long lived HIV immunocompromised patients AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV lifecycle and related cancers at the molecular level is required for novel strategies of molecularlymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein.
Blood, 1988
To analyze the pathogenesis of B-cell lymphomas in patients with acquired immunodeficiency syndrome (AIDS), we studied two cell lines, Es I and Es III, established from one such lymphoma for the presence of sequences of the Epstein-Barr virus (EBV) and the human immunodeficiency virus [HIV; lymphadenopathy-associated virus (LAV/HTLV-III)] as well as for the presence of cytogenetic abnormalities and monoclonal rearrangements of immunoglobulin and T-cell receptor genes. Both cell lines expressed the same IgM, kappa phenotype as the original lymphoma. The karyotype of Es I was 46, XY, t(8;14), 2 p+, inv (6p), 17p-, and the cells of Es III had an additional i(7q). Immunoglobulin gene studies demonstrated the identical monoclonal rearrangements in both cell lines. Neither EBV nor HIV sequences were detectable in the malignant B cells at the genomic level, leading to the conclusion that mechanisms other than transformation by EBV or HIV may have contributed to the B-cell lymphoma in this ...