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LETTER TO EDITOR Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 4  |  Page : 890-891
High incidence of Epstein-Barr virus infection in childhood acute lymphocytic leukemia


Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

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Date of Web Publication27-Oct-2010
 

How to cite this article:
Khan G. High incidence of Epstein-Barr virus infection in childhood acute lymphocytic leukemia. Indian J Pathol Microbiol 2010;53:890-1

How to cite this URL:
Khan G. High incidence of Epstein-Barr virus infection in childhood acute lymphocytic leukemia. Indian J Pathol Microbiol [serial online] 2010 [cited 2020 Nov 30];53:890-1. Available from: https://www.ijpmonline.org/text.asp?2010/53/4/890/72043


Sir,

We read with interest the article by Sehgal et al published in the last issue of this journal. [1] The authors studied the link between Epstein-Barr virus (EBV) and childhood acute lymphocytic leukemia (ALL). They reported that 32% of their cases were EBV positive and in 20%, there was evidence of viral replication.

Ever since its isolation in 1964 from a Burkitt's lymphoma cell line, EBV has continued to attract considerable attention. This was primarily due to its potent oncogenic properties and its association with an ever increasing number of human malignancies of both epithelial and lymphoid origin, including Burkitt's lymphoma, posttransplant lymphoproliferative disorders, undifferentiated nasopharyngeal carcinoma, and Hodgkin's lymphoma. [2] However, the precise role of EBV in the pathogenesis of most of these malignancies is unclear. Moreover, the fact that EBV is ubiquitous in the general population with over 90% of the people worldwide being seropositive, warrants caution when implicating this virus in the pathogenesis of any human disease. Thus, the mere detection of EBV in a clinical sample cannot be interpreted to indicate that the virus is etiologically involved. In this context, the study by Sehgal et al has to be interpreted with caution. We have several points that we would like to raise with reference to this study.

The authors studied 25 consecutive pediatric ALL cases seen in their institution. They showed that 8/25 (32%) of these were EBV positive as demonstrated by polymerase chain reaction (PCR). These findings are not surprising, considering the fact that PCR is an extremely sensitive technique and EBV is ubiquitous in the general population. What is surprising is that the authors did not find EBV in any of their controls (30 healthy laboratory controls, 22 age-matched disease controls, 12 cases of acute myeloid leukemia, and 15 cases of multiple myeloma). This is highly unusual and inconsistent with the previous reports. [3],[4],[5] It is generally accepted that EBV infects B cells and the frequency of the EBV-infected cells in healthy seropositive individuals varies from about 1-50 cells per 10 6 B cells. These EBV-infected cells can be readily detected using PCR. [3],[4],[5] Moreover, in certain malignancies and states of immunosuppression, EBV viral load increases considerably. [3],[4],[5],[6] However, Sehgal et al did not find a single positive case out of 79 cases, some of which were cancer patients and likely to have some degree of immune suppression.

Sehgal et al also reported that 5/25 (20%) of their ALL cases were positive for EBV-encoded ZEBRA protein by Western blot. However, the authors neither showed the data nor discussed those in their results. It is unclear whether the ZEBRA-positive cases were also EBV-PCR positive. ZEBRA is an indicator of EBV replication and it is not usually expressed in tumor cells of EBV-associated malignancies. One plausible explanation for ZEBRA positivity reported by Sehgal et al is that some EBV-infected cells, possibly as a result of reduced immune competence, are triggered into EBV-lytic cycle. [7] This would, however, imply that EBV is not causally associated with ALL, but rather it is a consequence of the disease. In order to demonstrate a causal relationship, the authors should have performed Epstein-Barr virus-encoded RNA -in situ hybridization on cytospins of lymphocytes from ALL cases to determine the cellular location of EBV. This technique has now become the gold standard for the detection of EBV in cytologic/histologic material and it will clearly show if the virus is present in the malignant cells, and therefore, potentially associated with the disease, or present in nonmalignant infiltrating lymphocytes, and therefore, a mere passenger.

 
   References Top

1.Sehgal S, Mujtaba S, Gupta D, Aggarwal R, Marwaha RK. High incidence of Epstein Barr virus infection in childhood acute lymphocytic leukemia: A preliminary study. Indian J Pathol Microbiol 2010;53:63-7.   Back to cited text no. 1
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2.Rickinson AB, Kieff E. Epstein-Barr virus. In: Knipe DM, Howley PM, editors. Fields Virology. 5 th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2006.   Back to cited text no. 2
    
3.Khan G, Miyashita EM, Yang B, Babcock GJ, Thorley-Lawson DA. Is EBV persistence in vivo a model for B cell homeostasis? Immunity 1996;5:173-9.   Back to cited text no. 3
    
4.Khan G, Lake A, Shield L, Freeland J, Andrew L, Alexander FE, et al. Phenotype and frequency of Epstein-Barr virus-infected cells in pretreatment blood samples from patients with Hodgkin lymphoma. Br J Haematol 2005;129:511-9.   Back to cited text no. 4
    
5.Njie R, Bell AI, Jia H, Croom-Carter D, Chaganti S, Hislop AD, et al. The effects of acute malaria on Epstein-Barr virus (EBV) load and EBV-specific T cell immunity in Gambian children. J Infect Dis 2009;199:31-8.   Back to cited text no. 5
    
6.Rose C, Green M, Webber S, Kingsley L, Day R, Watkins S, et al. Detection of Epstein-Barr virus genomes in peripheral blood B cells from solid-organ transplant recipients by fluorescence in situ hybridization. J Clin Microbiol 2002;40:2533-44.   Back to cited text no. 6
    
7.Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer 2004;4:757-68.  Back to cited text no. 7
    

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Correspondence Address:
Gulfaraz Khan
Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 17666
United Arab Emirates
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.72043

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