Abstract
Human endogenous retroviral sequences (HERVs) are believed to be possible pathogenic agents in carcinogenesis. HERV-K is the most biologically active form, since members of this family have intact open reading frames for the gag, pol or envgenes. Antibody response against HERV-K peptides has been reported in leukemia patients, suggesting a possible overexpression of this sequence in leukemic cells. Using real-time quantitative RT-PCR (TaqMan), we found that in six of the eight leukemia samples we collected, transcriptional activity of HERV-K10-like gag gene was 5- to 10-fold higher than in normal peripheral blood mononuclear cells (PBMCs) or mononuclear cells from cord blood. The overexpression was marked enough to be detected by Northern blot. In addition, there was no significant variation of HERV-K expression in normal PBMCs after exposure to different factors (PHA, gamma irradiation, 5-azacytidine) that potentially modulate HERV expression. This suggests that HERV-K relative overexpression in leukemia samples might be specifically associated with tumor development. The origin of these transcriptional variations is therefore worth being investigated further.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Wilkinson DA, Mager DL, Leong J-AC . Human endogenous retroviruses. In: Levy JA (ed.) The Retroviridae vol 3: Plenum Press: NY 1994 pp 465–535
Löwer R, Löwer J, Kurth R . The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences Proc Natl Acad Sci USA 1996 93: 5177–5184
Andersson G, Svensson AC, Setterblad N, Rask L . Retroelements in the human MHC class II regions Trends Genet 1998 14: 109–114
Dangel AW, Baker BJ, Mendoza CY, Mendoza AR, Yu CY . Complement component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus HERV-K(C4) are a molecular clock of evolution Immunogenetics 1995 42: 41–52
Ting CN, Rosenberg MP, Snow CM, Samuelson LC, Meisler MH . Endogenous retroviral sequences are required for tissue-specific expression of a human salivary amylase gene Genes Dev 1992 6: 1457–1465
Leib-Mösch C, Brack-Werner R, Werner T, Bachmann M, Faff O, Erfle V, Hehlmann R . Endogenous retroviral elements in human DNA Cancer Res 1990 50: 5636S–5642S
Leib-Mösch C, Bachman M, Brack-Werner R, Werner T, Erfle V, Hehlmann R . Expression and biological significance of human endogenous retroviral sequences Leukemia 1992 6: 72S–75S
Yoder JA, Walsh CP, Bestor TH . Cytosine methylation and the ecology of intragenomic parasites Trends Genet 1997 13: 335–340
Götzinger N, Sauter M, Roemer K, Mueller-Lantzsch N . Regulation of human endogenous retrovirus-K Gag expression in teratocarcinoma cell lines and human tumours J Gen Virol 1996 77: 2983–2990
Florl AR, Löwer R, Schmitz-Dräger BJ, Schulz WA . DNA methylation and expression of LINE-1 and HERV-K provirus sequences in urothelial and renal cell carcinomas Br J Cancer 1999 80: 1312–1321
Ono M, Yasunaga T, Miyata T, Shikubo U . Nucleotide sequence of human retrovirus genome related to the mouse mammary tumor virus genome J Virol 1986 60: 589–598
Tönjes RR, Czauderna Frank, Kurth R . Genome-wide screening, cloning, chromosomal assignment, and expression of full-length human endogenous retrovirus type K J Virol 1999 73: 9187–9195
Sauter M, Schommer S, Kremmer E, Remberger K, Dölken G, Lemm I, Buck M, Best B, Neumann-Haefelin D, Mueller-Lantzsch N . Human endogenous retrovirus K10: expression of Gag protein and detection of antibodies in patient with seminomas J Virol 1995 69: 414–421
Sauter M, Roemer K, Best B, Afting M, Schommer S, Seitz G, Hartmann M, Mueller-Lantzsch N . Specificity of antibodies directed against Env protein of human endogenous retroviruses in patients with germ cell tumors Cancer Res 1996 56: 4362–4365
Boyd MT, Foley B, Brodsky I . Evidence for copurification of HERV-K-related transcripts and a reverse transcriptase activity in human platelets from patients with essential thrombocythemia Blood 1997 90: 4022–4030
Brodsky I, Foley B, Haines D, Johnston J, Cuddy K, Gillespie D . Expression of HERV-K proviruses in human leukocytes Blood 1993 81: 2369–2374
Hehlmann R, Kister P, Willer A, Simon M, Schenk M, Seifarth W, Papakonstantinou G, Saussele S, Kolb HJ, Ansan H, Leib-Mösch C the German CML Study Group. Therapeutic progress and comparative aspects in chronic myelogenous leukemia (CML): interferon alpha vs hydroxyurea vs busulfan and expression of MMTV-related endogenous retroviral sequences in CML. German CML Study Group Leukemia 1994 8: S127–132
Hehlmann R, Willer A, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Queisser W, Loffler H, Hochhaus A, Tobler A, Lengfelder E, Berger U, Leib-Mösch C . Randomized studies with interferon in chronic myelogenous leukemia (CML) and comparative molecular aspects. German CML Study Group Leukemia 1997 11: 506–511
Denner J, Phelps RC, Löwer J, Löwer R, Kurth R . Expression of the human endogenous retrovirus HERV-K in tumor and normal tissues and antibody response of pregnant women, tumor and AIDS patients against HERV-K Gag and Env peptides AIDS Res Hum Retroviruses 1995 11: 103
Morse B, Rotherg PG, South VJ, Spandorfer JM, Astrin SM . Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma Nature 1988 333: 87–90
Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B, Nakamura Y . Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer Cancer Res 1992 52: 643–645
Wahbi K, Hayette S, Callanan M, Gadoux M, Charrin C, Magaug JP, Rimokh R . Involvement of a human endogenous retroviral sequence (THE-7) in a t(7;14)(q21;q32) chromosomal translocation associated with a B cell chronic lymphocytic leukemia Leukemia 1997 11: 1214–1219
Mangeney M, Heidmann T . Tumor cells expressing a retroviral envelope escape immune rejection in vivo Proc Natl Acad Sci USA 1998 95: 14920–14925
Mtrand P eds Linndskog M, Blomberg J . Expression of human endogenous retroviral sequences in peripheral blood mononuclear cells of healthy individuals J Gen Virol 1992 73: 2463–2466
Urnovitz H, Murphy W . Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease Clin Microbiol Rev 1996 9: 72–99
Chen RZ, Pettersson U, Beard C, Jackson-Grusby L, Jaenisch R . DNA hypomethylation leads to elevated mutation rates Nature 1998 395: 89–93
Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP . Alterations in DNA methylation: a fundamental aspect of neoplasia Adv Cancer Res 1998 72: 141–196
Wahlfor J, Hiltunen H, Heinonen K, Hämäläinen E, Alhonen L, Jänne J . Genomic hypomethylation in human chronic lymphocytic leukemia Blood 1992 80: 2074–2080
Acknowledgements
The authors thank the Service Commun de l'IFR 22 for access to the ABI PRISM 7700, and in particular Nathalie Jouy for her help with the quantitative method. We also thank the Service des Maladies du Sang du CHU de Lille for its participation in collecting samples, Pr Pierre Fenaux for critical reading and helpful comments and Geraldine Orazi for cord blood samples. S Depil received a grant from the Association pour la Recherche sur le Cancer.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Depil, S., Roche, C., Dussart, P. et al. Expression of a human endogenous retrovirus, HERV-K, in the blood cells of leukemia patients. Leukemia 16, 254–259 (2002). https://doi.org/10.1038/sj.leu.2402355
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2402355
Keywords
This article is cited by
-
HERV-K (HML-2) insertion polymorphisms in the 8q24.13 region and their potential etiological associations with acute myeloid leukemia
Archives of Virology (2023)
-
Human endogenous retrovirus, HERV-P and HERV-R in pediatric leukemia patients
Journal of Hematopathology (2019)
-
Screening for viral nucleic acids in vestibular schwannoma
Journal of NeuroVirology (2018)
-
Expression of the pol gene of human endogenous retroviruses HERV-K and -W in leukemia patients
Archives of Virology (2017)
-
Construction of a molecular clone of ovine enzootic nasal tumor virus
Virology Journal (2016)