OJPed  Vol.3 No.1 , March 2013
Myelodysplastic syndrome (MDS) associated with EBV infection in a pediatric patient
Abstract: Background: Epstein Barr Virus (EBV) is associated with different kinds of tumors. In the present study we tried to understand its role in pediatric MDS of a 4-year-old girl with EBV infection and MDS with refractory anemia and monosomy 7. Procedures: The work-up included: hematological tests; serology for IgM, IgG antibodies to EBV; PCR for EBV; cytogenetics of bone marrow (BM), and FISH analysis of BM and blood; immunohistochemistry-LMP1 expression on BM smears. Results: Hematological follow up showed constant mild dysplastic changes mostly in the erythroid lineage. PCR for EBV showed positive results in the nasopharygeal smears as well as in blood 15 weeks after disease onset. Cytogenetic analysis showed monosomy7 inall the mitoses of BM sample. Fluorescence in situ hybridization (FISH) showed monosomy 7% in 57% of the cells, followed by a decreased tendency in the percentage of monosomy 7 cells in both BM and blood. Immunohistochemistry for EBV-latent membrane protein 1 (LMP-1) on the patient’s BM smears, 21 weeks post disease onset, showed 9% positive cells, 80% of them carried monosomy 7. Conclusion: The parallel occurrence of the EBV infection and MDS, as well as the continuous EBV PCR positive and monosomy 7, support the possibility that they are related.
Cite this paper: Manor, E. , Shemer-Avni, Y. , Boriakovski, S. , Kafka, M. , Bodner, L. and Kapelushnik, J. (2013) Myelodysplastic syndrome (MDS) associated with EBV infection in a pediatric patient. Open Journal of Pediatrics, 3, 28-34. doi: 10.4236/ojped.2013.31006.

[1]   Niemeyer, C.M. and Baumann, I. (2008) Myelodysplastic syndrome in children and adolescence. Seminars in Hematology, 45, 60-70. doi:10.1053/j.seminhematol.2007.10.006

[2]   Mitelman, F. and Heim, S. (1992) Quantitative acute leukemia cytogenetics. Genes Chromosomes & Cancer, 5, 57-66. doi:10.1002/gcc.2870050109

[3]   Johansson, B., Mertens, F. and Mitelman, F. (1993) Cytogenetic deletion maps of hematologic neoplasms; Circumstantial evidence for tumor suppressor loci. Genes Chromosomes & Cancer, 8, 205-218. doi:10.1002/gcc.2870080402

[4]   Luna-Fineman, S., Shannon, K.M. and Lange, B.J. (1995) Childhood monosomy 7: Epidemyology, biology and mechanistic implications. Blood, 85, 1985-1999.

[5]   Sieff, C., Chessells, J., Harvey, A., et al. (1981) Monosomy 7 in childhood: A myeloproliferative disorder. British Journal of Haematology, 49, 235-249. doi:10.1111/j.1365-2141.1981.tb07220.x

[6]   Hasle, H., Arico, M., Basso, G., et al. (1999) Myelodysplastic syndrom, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. Leukemia, 13, 376-385. doi:10.1038/sj.leu.2401342

[7]   Kardos, G., Bumann, I., Passmore, S.I., et al. (2003) Refractory anemia in childhood: A retrospective analysis of 67 patients with particular reference to monosomy 7. Blood, 102, 1997-2003. doi:10.1182/blood-2002-11-3444

[8]   Johnson, E. and Cotter, F. (1997) Monosomy 7 and 7qassociated with myeloid malignancy. Blood Reviews, 11, 46-55. doi:10.1016/S0268-960X(97)90006-0

[9]   Hall, G.W. (2001) Childhood myeloid leukemias. Best Practice & Research Clinical Haematology, 14, 573-591. doi:10.1053/beha.2001.0155

[10]   Epstein, M.A., Achong, B.G. and Barr, S.Y.M. (1964) Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet, 1, 702-703. doi:10.1016/S0140-6736(64)91524-7

[11]   Williams, H. and Crawford, D.H. (2006) Epstein-Barr virus: The impact of scientific advances on clinical practice. Blood, 107, 862-869. doi:10.1182/blood-2005-07-2702

[12]   Middeldorp, J.M., Brink, A.A., van den Brule, A.J., et al. (2003) Pathogenic roles for Epstein-Bar virus (EBV) gene products in EBV-associated proliferative disorders. Critical Reviews in Oncology Hematology, 45, 1-36. doi:10.1016/S1040-8428(02)00078-1

[13]   Geiger, T.R. and Martin, J.M. (2006) The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2 phosphorylation and interferon signaling in human B cells. Jounal of Virology, 80, 11638-11650. doi:10.1128/JVI.01570-06

[14]   Herrod, H., Dow, L. and Sullivan, J. (1983) Persitant Epstien Barr virus infection mimicking juvenile chronic myelogenous leukemia: Immunologic and hemathologic studies. Blood, 61, 1098-1104.

[15]   Kirby, M.A., Weitzman, S. and Freedman, N.H. (1990) Juvenile chronic myelogenous leukemia: Differentiation from infantile cytomegalovirus infection. Journal of Pediatric Hematology Oncology, 12, 292-296. doi:10.1097/00043426-199023000-00007

[16]   Lorenzan, L., Lyons, H., Sawaf, H., et al. (2002) Human herpes virus 6 infection mimicking juvenile chronic myelogenous leukemia in an infant. Journal of Pediatric Hematology Oncology, 24, 136-141. doi:10.1097/00043426-200202000-00016

[17]   Shaffer, L.G., Slovak, M.L. and Campbell, L.J., Eds. (2009) An international system for human cytogenetic nomenclature. S. Karger, Basel.

[18]   Niesters, H.G., Van Esser, J., Fries, E., et al. (2000) Development of a real-time quantitative assay for detection of Epstein-Barr virus. Journal of Clinical Microbiology, 38, 712-715.

[19]   Parkin, D.M. (2003) The global health burden of infection-associated cancers in the year 2002 (review). International Journal of Cancer, 118, 3030-3040. doi:10.1002/ijc.21731

[20]   Cohen, J.I. (2000) Epstein-Barr virus infection. New England Journal of Medicine, 343, 481-492. doi:10.1056/NEJM200008173430707

[21]   Leibowitz, D. (1998) Epstein-Bar virus and a cellular signaling pathway in lymphomas from immunosuppressed patients. New England Journal of Medicine, 338, 1413-1421. doi:10.1056/NEJM199805143382003

[22]   Dukers, D.F., Jaspars, L.H., Vos, W., et al. (2000) Quantitative immunohistochemical analysis of cytokine profiles in Epstein-Barr virus-positive and negative cases of Hodgkin’s disease. Journal of Pathology, 190, 143-149. doi:10.1002/(SICI)1096-9896(200002)190:2<143::AID-PATH519>3.0.CO;2-5

[23]   Khabir, A., Karray, H., Rodriguez, S., et al. (2005) EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas. Virology Journal, 2, 39. doi:10.1186/1743-422X-2-39

[24]   Mowry, S.E., Strocker, A.M., Chan, J., et al. (2008) Immunohistochemical analysis and Epstein-Barr virus in the tonsils of transplant recipients and healthy controls. Archives of Otolaryngology-Head & Neck Surgery, 134, 936-939. doi:10.1001/archotol.134.9.936

[25]   Hasle, H. and Niemeyer, C.M. (2002) Myelodysplastic syndrome and juvenile myelomonocytic leukemia in children. In: Bennett, J.M., Ed., The Myelodysplastic Syndromes: Pathology and Clinical Management, Marcel Dekker Inc., New York, 299-344.

[26]   Platzbecker, M., Meredyth-Stewart, M. and Eninger, G. (2007) The pathogenesis of meylodysplatic syndromes (MDS). Cancer Treatment Reviews, 33, S53-S58. doi:10.1016/j.ctrv.2007.07.021

[27]   Bejar, R. and Ebert, B.L. (2010) The genetic basis of myelodysplatic syndromes. Hematology-Oncology Clinics of North America, 24, 295-315. doi:10.1016/j.hoc.2010.02.001

[28]   Kwong, Y.L., Ng, M.H. and Ma, S.K. (2000) Familial acute myeloid leukemia with monosomy 7: Late onset and involvement of a multipotential progenitor cell. Cancer Genetics and Cytogenetics, 116, 170-173. doi:10.1016/S0165-4608(99)00121-1

[29]   Kwong, Y.L. and Chan, L.C. (1994) Involvement of eosinophils in acute myeloid leukemia with monosomy 7 demonstrated by in situ hybridization. British Journal of Haematology, 88, 389-391. doi:10.1111/j.1365-2141.1994.tb05035.x

[30]   Shannon, K.M., Turhan, A.G., Rogers, P.C.J., et al. (1992) Evidence implicating heterozygous deletion of chromosome 7 in the pathogenesis of familial leukemia associated with monosomy 7. Genomics, 80, 332-336.

[31]   Harrison, K.J., Massing, B., McKenna, C., et al. (1995) Molecular cytogenetic analysis of monosomy 7 in pediatric patients with myelodysplastic syndrome. American Journal of Hematology, 48, 88-91. doi:10.1002/ajh.2830480204

[32]   Leong, A.S.Y., Cooper, K., Joel, F. and Leong, W.M. (1999) Manual of diagnostic antibodies for immunohistology. Oxford University Press, Oxford, 162.

[33]   Mahoney Jr., D.H., McClain, K.L., Hanson, I.C., et al. (1989) Acquired immune deficiency, myelodysplasia and acute nonlymphocytic leukemia associated with monosomy 7 and t(3;3) (q21;q26) in a child with langerhans cell histocytosis. American Journal of Pediatric Hematology, 11, 153-157.

[34]   Manabe, A., Yoshimasu, T., Ebihara, Y., et al. (2004) Viral infection in juvenile myelomonocytic leukemia: Prevalence and clinical implications. Journal of Pediatric Hematology Oncology, 26, 636-641. doi:10.1097/01.mph.0000140653.50344.5c

[35]   Stollmann, B., Fonatsch, C.H. and Havers, W. (1985) Persistent Epstein-Barr virus infection associated with monosomy 7 or chromosome 3 abnormality in childhood myeloproliferative disorders. British Journal of Haematology, 60, 183-196. doi:10.1111/j.1365-2141.1985.tb07399.x

[36]   Straus, S.E. (1998) The chronic mononucleosis syndrome. Journal of Infectious Diseases, 157, 280-286.

[37]   Kimura, H., Hohino, Y., Kanegane, H., et al. (2001) Clinical and virologic characteristics of chronic Epstein-Barr virus infection. Blood, 98, 280-286. doi:10.1182/blood.V98.2.280

[38]   Borze, I., Scheinin, I., Sitonen, S., et al. (2011) miRNA expression profiles in myelodysplastic syndromes reveal Epstein-Barr virus miR-BART 13 dysregulation. Leukemia & Lymphoma, 52, 1567-1573. doi:10.3109/10428194.2011.568652