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Blood, 1 July 2004, Vol. 104, No. 1, pp. 9. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cornelissen, J. J. Search for Related Content PubMed Articles by Cornelissen, J. J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Molecular monitoring of EBV-positive lymphoma Jan J. Cornelissen ERASMUS UNIVERSITY MEDICAL CENTER, ROTTERDAM Monitoring of Epstein-Barr virus DNA by quantitative real-time polymerase chain reaction may serve as an accurate surrogate marker of tumor load in patients with Hodgkin and non-Hodgkin lymphoma that were demonstrated to be EBV-positive. Epstein Barr virus (EBV) is a widespread human herpesvirus that establishes lifelong asymptomatic infection of B cells. In 1997, EBV was classified by the World Health Organization–International Agency for Research on Cancer (WHO-IARC) as a group I human carcinogen because of its etiologic role in nasopharyngeal carcinoma and lymphomagenesis. EBV is associated with endemic Burkitt lymphoma, posttransplantation lymphoproliferative disease (PTLD), some T-cell and natural killer (NK) cell lymphomas, and Hodgkin disease. While the exact role of EBV in the pathogenesis of each type of lymphoma still needs to be elucidated,1 epidemiologic studies have shown strong associations between infectious mononucleosis and EBV-positive Hodgkin disease2 and also between posttransplantation EBV reactivation and the development of PTLD.3 Molecular monitoring of EBV DNA levels in patients with PTLD has been shown to accurately and sensitively reflect disease activity and is currently used to tailor treatment for the individual patient. Although viral infection is a presumed source of EBV DNA in patients with PTLD, release of EBV fragments from tumor cells, instead of fully assembled viral particles, is likely to play a major role in established PTLD. Standard curves for quantification of EBV DNA. See the complete figure in the article beginning on page 243.   The hypothesis that release of EBV DNA fragments from EBV-positive lymphomas might be a general phenomenon and might be used as a surrogate marker of disease activity was the starting point for the study of Au and colleagues reported in this issue of Blood (page 243). The authors show that molecular monitoring of EBV DNA by quantitative real-time polymerase chain reaction (PCR) closely mirrors the clinical picture of the individual patient with an EBV-positive lymphoma. In addition, patients with a high EBV DNA copy number before the start of treatment showed inferior outcome. The prognostic significance of quantified EBV DNA seemed independent from the type of lymphoma, but was especially evident in patients with NK cell lymphoma. These results compare well to earlier findings in patients with PTLD and suggest that patients with non-Hodgkin lymphoma as well as patients with Hodgkin disease should be evaluated for the presence of EBV at diagnosis and during follow-up if EBV positivity has been demonstrated. Such diagnostic evaluation may include in situ hybridization for EBV-encoded RNA (EBER) on histopathologic examination and the quantification of EBV DNA in plasma by PCR. Au et al used a very sensitive real-time PCR and reported relatively high values of EBV DNA in the NK cell lymphoma and PTLD group. The copy numbers reported exceed those reported in PTLD by a number of other investigators. The different quantified levels of EBV DNA hamper the comparison and combined analysis of several studies. It strongly supports efforts aimed at standardization of recently used real-time technology, such as has been initiated by the Quality Control for Molecular Diagnostics (QCMD, www.qcmd.org). Furthermore, the data presented by Au et al emphasize the importance of studies aiming to elucidate the exact pathogenetic role of EBV in lymphomagenesis, as such studies may yield new targets for therapy in poor-risk EBV-positive lymphoma. So far, the interplay between the EBV gene program, type and developmental stage of infected lymphocyte, and putative additional oncogenic event has remained an open but intriguing question in most EBV-positive lymphomas. References Thorley-Lawson DA, Gross A. Persistence of the Epstein-Barr Virus and the origins of associated lymphomas. N Eng J Med. 2004;350: 1328-1337.[Free Full Text] Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Eng J Med. 2003;349: 1324-1332.[Abstract/Free Full Text] Van Esser JWJ, van der Holt B, Meijer E, et al. Epstein-Barr virus reactivation is a frequent event after allogeneic hematopoietic stem cell transplantation and quantitatively predicts EBV-lymphoproliferative disease following T-cell depleted stem cell transplantation. Blood. 2001;98: 972-978.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients Wing-Yan Au, Annie Pang, Carolyn Choy, Chor-Sang Chim, and Yok-Lam Kwong Blood 2004 104: 243-249. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cornelissen, J. J. Search for Related Content PubMed Articles by Cornelissen, J. J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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