Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study

Infectious Agents and Cancer

Aouni Mahjoub¹  Feki Salma⁴  Agut Henri³  Khelif Abderrahim²  Zaier Monia²  Abid Ben Salem Nabil¹  Ben Fredj Nadia¹  Gautheret-Dejean Agnès³  Nefzi Faten¹ 

[1] Laboratory of Transmissible Diseases and Biological Active Substances, LR99-ES27, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia;Department of Clinical Hematology, Farhat Hached Hospital, Sousse, Tunisia;Laboratory of Virology, Pitié-Salpêtrière Hospital AP-HP, Paris, France;Department of Clinical Biology, Faculty of Pharmacy, Monastir, Tunisia

关键词: Chemotherapy;    Whole blood;    Bone marrow;    Viral load;    Acute leukemia;    Human herpesvirus-6;   

Others  :  803340
DOI  :  10.1186/1750-9378-7-31

 received in 2012-07-05, accepted in 2012-10-31,  发布年份 2012

【 摘 要 】

Background

Infectious etiology in lymphoproliferative diseases has always been suspected. The pathogenic roles of human herpesvirus-6 (HHV-6) in acute leukemia have been of great interest. Discordant results to establish a link between HHV-6 activation and the genesis of acute leukemia have been observed. The objective of this study was to evaluate a possible association between HHV-6 infection and acute leukemia in children and adults, with a longitudinal follow-up at diagnosis, aplasia, remission and relapse.

Methods

HHV-6 load was quantified by a quantitative real-time PCR in the blood and bone marrow samples from 37 children and 36 adults with acute leukemia: 33 B acute lymphoblastic leukemia (B-ALL), 6 T acute lymphoblastic leukemia (T-ALL), 34 acute myeloid leukemia (AML).

Results

HHV-6 was detected in 15%, 8%, 30% and 28% of the blood samples at diagnosis, aplasia, remission and relapse, respectively. The median viral loads were 138, 244, 112 and 78 copies/million cells at diagnosis, aplasia, remission and relapse, respectively. In the bone marrow samples, HHV-6 was detected in 5%, 20% and 23% of the samples at diagnosis, remission and relapse, respectively. The median viral loads were 34, 109 and 32 copies/million cells at diagnosis, remission and relapse, respectively. According to the type of leukemia at diagnosis, HHV-6 was detected in 19% of the blood samples and in 7% of the bone marrow samples (with median viral loads at 206 and 79 copies/million cells, respectively) from patients with B-ALL. For patients with AML, HHV-6 was present in 8% of the blood samples and in 4% of the bone marrow samples (with median viral loads at 68 and 12 copies/million cells, respectively). HHV-6 was more prevalent in the blood samples from children than from adults (25% and 9%, respectively) and for the bone marrow (11% and 0%, respectively). All typable HHV-6 were HHV-6B species. No link was shown between neither the clinical symptoms nor the abnormal karyotype and HHV-6 activation. A case of HHV-6 chromosomal integration was shown in one patient with AML.

Conclusion

This study confirms the absence of role of HHV-6 in the genesis of acute leukemia but the virus was reactivated after chemotherapy treatment.

【 授权许可】

   
2012 Faten et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Salahuddin SZ, Ablashi DV, Markham PD, Josephs SF, Sturzenegger S, Kaplan M, Halliga G, Biberfeld P, Wong-Staal F, Kramarsky B: Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986, 234:596-601.
• [2]Ablashi D, Agut H, Berneman Z, Campadelli-Fiume G, Carrigan D, Ceccerini-Nelli L, Krueger G, Kramarsky B, Salahuddin R, Gallo R: Human herpesvirus-6 strain groups: a nomenclature. Arch Virol 1993, 129:363-366.
• [3]DeBolle I, Naesens L, De Clercq E: Update on human herpesvirus-6 biology, clinical features and therapy. Clin Microbiol Rev 2005, 18:217-245.
• [4]Hara T, Suzuki Y, Semba T, Hatanaka M, Matsumoto M, Seya T: High expression of membrane cofactor protein of complement (CD46) in human leukemia cell lines: Implication of an alternatively spliced form containing the STA domain in CD46 upregulation. Scand J Immunol 1995, 42:581-590.
• [5]Razzaque A: Oncogenic potential of human herpesvirus-6 DNA. Oncogene 1990, 5:1365-1370.
• [6]Kashanchi F, Araujo J, Donige J, Muralidhar S, Hoch R, Khlei S, Mendelson E, Thompson J, Azumi N, Brady JN, Luppi M, Torelli G, Rosenthal JL: Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53. Oncogene 1997, 14:359-367.
• [7]Lacroix A, Collot-Teixeira S, Mardivirin L, Jaccard A, Petit B, Piquet C, Sturtz F, Preux PM, Bordessoul D, Ranger-Rogez S: Involvement of Human Herpesvirus-6 variant B in classic Hodghkin’s lymphoma via DR7 oncoprotein. Clin Cancer Res 2010, 16:4711-4721.
• [8]Daibata M, Taguchi T, Sawada T: Chromosomal transmission of human herpesvirus 6 DNA in acute lymphoblastic leukaemia. Lancet 1998, 352:543-544.
• [9]Morissette G, Flamand L: Herpesviruses and chromosomal integration. J Virol 2010, 84:12100-12109.
• [10]Luka J, Pirruccello SJ, Kersey JH: HHV-6 genome in T-cell acute lymphoblastic leukemia. Lancet 2007, 338:1277-1278.
• [11]Ohyashiki JH, AbeK Ojima T, Wang P, Zhou CF, Suzuki A, Ohyashiki K, Yamamoto K: Quantification of human herpesvirus 6 in healthy volunteers and patients with lymphoproliferative disorders by PCR-ELISA. Leuk Res 1999, 23:625-630.
• [12]Hermouet S, Sutton CA, Rose TM, Garand R, Neves AM, Bataile R, Casey JW, Corre l: Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma. Leukemia 2003, 17:185-195.
• [13]Barozzi P, Luppi M, Marasca R, Trovato R, Ceccherini-Nelli L, Torelli G: Human herpesvirus-6 genome in acute lymphoblastic leukemia: Evidence against an etiologic relationship. Acta Haematol 1995, 94:169-172.
• [14]Seror E, Coquerel B, Gautheret-Dejean A, Ballerini P, Landman-Parker J, Leverger G, Schneider P, Vannier JP: Quantitation of human herpes virus 6 genome in children with acute lymphoblastic leukemia. J Med Virol 2008, 80:689-693.
• [15]Andre-Garnier E, Milpied N, Boutolleau D, Saiagh S, Billaudel S, Imbert-Marcille BM: Reactivation of human herpesvirus 6 during ex vivo expansion of circulating CD34+ haematopoietic stem cells. J Gen Virol 2004, 85:3333-3336.
• [16]Hubacek P, Muzikova K, Hrdlickova A, Cinek O, Hyncicova K, Hrstkova H, Sedlacek P, Stary J: Prevalence of HHV-6 integrated chromosomallyamong children treated for acute lymphoblastic or myeloid leukemia in the Czech Republic. J Med Virol 2009, 81:258-263.
• [17]Tanaka-Taya K, Sashihara J, Kurahashi H, Amo K, Miyagawa H, Kondo K, Okada S, Yamanishi K: 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, 73:465-473.
• [18]Géraudie B, Charrier M, Bonnafous P, Heurté D, Desmonet M, Bartoletti MA, Penasse A, Henri A, Gautheret-Dejean A: Quantitation of Human Herpesvirus-6A, -6B and −7 DNAs in whole blood, monuclear and polymophonuclear cell fraction from healthy donors. J Clin Virol 2012, 53:151-155.
• [19]Leong H, Tuke P, Tedder R, Khanom A, Eglin R, Atkinson C, Ward N, Griffiths P, Clark A: The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol 2007, 79:45-51.
• [20]Ward K, Leong H, Nacheva E, Howard J, Atkinson C, Davies N, Griffiths P, Clark A: Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J Clin Microbiol 2006, 44:1571-1574.
• [21]Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, Dhedin N, Vernant JP, Henri A: Development of a real-time polymerase chain reaction assay for diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Methods 2002, 100:27-35.
• [22]Laurendeau I, Bahuau M, Vodovar N, Larramendy C, Olivi M, Bieche I, Vidaud M, Vidaud D: TaqMan PCR-based gene dosage assay for predictive testing in individuals from a cancer family with INK4 locus haploinsufficiency. Clin Chem 1999, 45:982-986.
• [23]Boutolleau D, Duros C, Bonnafous P, Caiola D, Karras A, De Castro N, Gueudin M, Henri A, Gautheret A: Identification of human herpesvirus 6 variant A and B by primer-specific real-time PCR may help to revisit their respective role in pathology. J Clin Virol 2006, 35:257-263.