Document Type : Research articles

Authors

1 Pediatric Hematologist-Oncologist, Shiraz University of Medical Sciences, Shiraz, Iran

2 Master of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran

3 PhD in Virology, Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Previous studies have pointed to the major role of viruses in the pathogenesis of cancers, especially lymphoproliferative cancers.
Objectives: The current study investigated the relationship between recent Human Herpesvirus Type 6 (HHV6) infection and childhood leukemia-lymphoma syndrome.
Methods: From January 2011 to December 2012, we entered every new case of acute lymphoblastic leukemia, non-Hodgkin lymphoma, acute myeloblastic leukemia, and Hodgkin lymphoma as the case group (n=48); moreover, 60 patients were randomly selected as controls from hospitalized children without infectious agents and myocarditis in the department of pediatric cardiology in Shiraz, Iran. Immunophenotyping of bone marrow or lymph node biopsy was performed for the case group. The DNA was extracted from all collected samples using a DNA extraction kit (Invitek Company, Germany), and a Real-time quantitative polymerase chain reaction (qPCR) for the U38 gene of HHV-6 was performed for the detection of the HHV-6 genome for both groups.
Results: In the case group, 48 patients with the age range of 0-18 years were assigned to four subgroups: 1- Acute Lymphoblastic Leukemia, 2- Acute Myeloblastic Leukemia, 3- Hodgkin Lymphoma, and 4- non-Hodgkin Lymphoma. In the case group, there were four positive HHV-6 PCR patients: One in Acute Lymphoblastic Leukemia, one in Non-Hodgkin Lymphoma, and two patients in the Hodgkin Lymphoma subgroup. None of the patients with T-cell leukemia-lymphoma had positive PCR. The frequency of HHV6 PCR positive was not significantly different between the case (8.3%) and control (1.6%) groups (P=0.169). No HHV-6 PCR positive was detected in T-cell leukemia/lymphoma patients.
Conclusion: As evidenced by the results of the present study, HHV-6 infection has no significant difference in children with T-Cell leukemia-lymphoma and healthy people.

Keywords

  1. Bispo JA, Pinheiro PS, Kobetz EK. Epidemiology and etiology of leukemia and lymphoma. Cold Spring Harb Perspect Med. 2020;10(6):1-22. doi: 10.1101/cshperspect.a034819. [PubMed: 31727680].
  2. Dursun R, Temiz SA. The clinics of HHV‐6 infection in COVID‐19 pandemic: pityriasis rosea and Kawasaki disease. Dermatol Ther. 2020;33(4):1-3. doi: 10.1111/dth.13730. [PubMed: 32475003].
  3. Handous I, Achour B, Marzouk M, Rouis S, Hazgui O, Brini I, et al. Co-infections of human herpesviruses (CMV, HHV-6, HHV-7 and EBV) in non-transplant acute leukemia patients undergoing chemotherapy. Virol J. 2020;17(1):1-5. doi: 10.1186/s12985-020-01302-4. [PubMed: 32183884].
  4. Tanaka‐Taya K, Sashihara J, Kurahashi H, Amo K, Miyagawa H, Kondo K, et al. Human herpesvirus 6 (HHV‐6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV‐6 DNA. J Med Virol. 2004;73(3):465-73. doi: 10.1002/jmv.20113. [PubMed: 15170644].
  5. Aimola G, Beythien G, Aswad A, Kaufer BB. Current understanding of human herpesvirus 6 (HHV-6) chromosomal integration. Antiviral Res. 2020;176:104720. doi: 10.1016/j.antiviral.2020.104720. [PubMed: 32044155].
  6. Farrell PJ. Epstein–Barr virus and cancer. Annu Rev Pathol. 2019;14:29-53. doi: 10.1146/annurev-pathmechdis-012418-013023. [PubMed: 30125149].
  7. He JR, Ramakrishnan R, Hirst JE, Bonaventure A, Francis SS, Paltiel O, et al. Maternal infection in pregnancy and childhood leukemia: a systematic review and meta-analysis. J Pediatr. 2020;217:98-109. doi: 10.1016/j.jpeds.2019.10.046. [PubMed: 31810630].
  8. Zhen Z, Bradel-Tretheway B, Sumagin S, Bidlack JM, Dewhurst S. The human herpesvirus 6 G protein-coupled receptor homolog U51 positively regulates virus replication and enhances cell-cell fusion in vitro. J Virol. 2005;79(18):11914-24. doi: 10.1128/JVI.79.18.11914-11924.2005. [PubMed: 16140767].
  9. Salonen MJ, Siimes MA, Salonen EM, Vaheri A, Koskiniemi M. Antibod status to HHV-6 in children with leukaemia. Leukemia. 2002;16(4):716-9. doi: 10.1038/sj.leu.2402437. [PubMed: 11960354].
  10. Shiramizu B, Chang CW, Cario MS. Absence of human hervpes-6 genome by polymerase chain reaction in children with hodgkin disease: A children's cancer Group Lymphoma Biology study. J Pediatr Hematol Oncol. 2001;23(5) 282-5. doi: 10.1097/00043426-200106000-00009. [PubMed: 11464983].
  11. Loutfy SA, Fawzy M, El-wakil M, Moneer MM. Presence of Human Herpes Virus 6 (HHV6) in Pediatric Lymphomas: impact on Clinical Course and association with Cytomeglovirus infection. Virol J. 2010;7:1-9. doi: 10.1186/1743-422X-7-287. [PubMed: 20979645].
  12. Seror E, Coquerel B, Gautheret-Dejean A, Ballerini P, Landman-Parker J, et al. Quantitation of human herpes virus 6 genome in children with acute lymphoblastic leukemia. J Med Virol. 2008;80(4):689-93. doi: 10.1002/jmv.21118. [PubMed: 18297709].
  13. Hubacek P, Muzikova K, Hrdlickova A, Cinek O, Hyncicova K, Hrstkova H, et al. Prevalence of HHV-6 integrated chromosomally among children treated for acute lymphoblastic or myeloid leukemia in the Czech Republic. J Med Virol. 2009;81(2):258-63. doi: 10.1002/jmv.21371. [PubMed: 19107978].
  14. Arzanian MT, Shahriari M, Rahiminejad MS. Deliberation of malignant cell DNA and correlation with relapse in ALL. Pajoohandeh. 2006;11:25-9.