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Article

Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia

  • Authors:
    • Mehran Haeri
    • Youjun Li
    • Yanmei Li
    • Qi Li
    • David E. Spaner
    • Yaacov Ben-David
  • View Affiliations / Copyright

    Affiliations: Department of Medical Biophysics, University of Toronto, Toronto, Canada, Division of Molecular and Cellular Biology, Sunnybrook Health Sciences Centre, Toronto, Canada, Norman Bethune College of Medicine, Jilin University, Changchun, P.R. China
  • Pages: 169-176
    |
    Published online on: May 16, 2013
       https://doi.org/10.3892/ijo.2013.1943
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Abstract

Identification of retrovirus integration sites is a powerful method to identify cancer-related genes. This approach led to the discovery of the Friend murine leukemia virus (F-MuLV) integration site-1 (fli-1). Viral insertion at the fli-1 locus induces erythroleukemia in susceptible strains of mice. Our recent data demonstrated that, F-MuLV-infected SCID mice, in contrast to wt CB17 controls, developed a non‑erythroleukemic leukemia without viral integration at the fli-1 locus. Using ligation-mediated polymerase chain reaction (LM-PCR) approach we identified a total of 15 viral integration sites in F-MuLV-infected SCID mice. One of the identified insertion sites was located about 62 kb upstream of the myeloblastosis (myb) gene. While integration within or surrounding the myb gene has been reported before for murine leukemia viruses, the location of the viral integration site identified in F-MuLV‑infected SCID mice is novel and has never been reported. Using PCR analysis we showed that viral integration at the myb locus occurs with a frequency of 35% and therefore is considered as a common integration site. Integration of F-MuLV in this locus resulted in upregulation of the MYB protein. Flow cytometry analysis and methylcellulose culture of leukemic cells isolated from tumors with viral integration close to the myb indicated tumors of myeloid origin. Our findings indicate that, in contrast to wt CB17 mice, F-MuLV-infected SCID mice display viral integration within myeloid specific gene loci that result in the development of myelogenous leukemia.
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1. 

Neil JC and Cameron ER: Retroviral insertion sites and cancer: fountain of all knowledge? Cancer Cell. 2:253–255. 2002. View Article : Google Scholar : PubMed/NCBI

2. 

Tamir A, Howard J, Higgins RR, Li Y, Berger L, Zacksenhaus E, Reis M and Ben-David Y: Fli-1, an Ets-related transcription factor, regulates erythropoietin-induced erythroid proliferation and differentiation: evidence for direct transcriptional repression of the Rb gene during differentiation. Mol Cell Biol. 19:4452–4464. 1999.

3. 

Ben-David Y, Prideaux VR, Chow V, Benchimol S and Bernstein A: Inactivation of the p53 oncogene by internal deletion or retroviral integration in erythroleukemic cell lines induced by Friend leukemia virus. Oncogene. 3:179–185. 1988.PubMed/NCBI

4. 

Li YJ, Higgins RR, Pak BJ, Shivdasani RA, Ney PA, Archer M and Ben-David Y: p45(NFE2) is a negative regulator of erythroid proliferation which contributes to the progression of Friend virus-induced erythroleukemias. Mol Cell Biol. 21:73–80. 2001. View Article : Google Scholar : PubMed/NCBI

5. 

Cui JW, Li YJ, Sarkar A, Brown J, Tan YH, Premyslova M, Michaud C, Iscove N, Wang GJ and Ben-David Y: Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation. Blood. 110:2631–2640. 2007.PubMed/NCBI

6. 

Shaked Y, Cervi D, Neuman M, Pak B, Kerbel RS and Ben-David Y: Splenic microenvironment is a source of angiogenesis/inflammatory mediators accelerating the extra-medullary expansion of murine erythroleukemic cells. Blood. 105:4500–4507. 2005.

7. 

Oliff AI, Hager GL, Chang GH, Scolnick EM, Chan HW and Lowy DR: Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus. J Virol. 33:475–486. 1980.PubMed/NCBI

8. 

Moreau-Gachelin F, Tavitian A and Tambourin P: Spi-1 is a putative oncongene in virally induced murine erythroleukemias. Nature. 331:277–280. 1988. View Article : Google Scholar : PubMed/NCBI

9. 

Ben-David Y, Giddens EG, Letwin K and Bernstein A: Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev. 5:908–918. 1991. View Article : Google Scholar : PubMed/NCBI

10. 

Wolff L: Myb-induced transformation. Crit Rev Oncog. 7:245–260. 1996. View Article : Google Scholar : PubMed/NCBI

11. 

Moreau-Gachelin F, Wendling F, Molina T, Denis N, Titeux M, Grimber G, Briand P, Vainchenker W and Tavitian A: Spi-1/PU. 1 transgenic mice develop multistep erythroleukemias. Mol Cell Biol. 16:2453–2463. 1996.PubMed/NCBI

12. 

Hasegawa M, Yamaguchi S, Aizawa S, Ikeda H, Tatsumi K, Noda Y, Hirokawa K and Kitagawa M: Resistance against Friend leukemia virus-induced leukemogenesis in DNA-dependent protein kinase (DNA-PK)-deficient scid mice associated with defective viral integration at the Spi-1 and Fli-1 site. Leukemia Res. 29:933–942. 2005. View Article : Google Scholar : PubMed/NCBI

13. 

Daniel R, Katz RA and Skalka AM: A role for DNA-PK in retroviral DNA integration. Science. 284:644–647. 1999. View Article : Google Scholar : PubMed/NCBI

14. 

Daniel R, Katz RA, Merkel G, Hittle JC, Yen TJ and Skalka AM: Wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses. Mol Cell Biol. 21:1164–1172. 2001. View Article : Google Scholar : PubMed/NCBI

15. 

Wurtele H, Little KCE and Chartrand P: Illegitimate DNA integration in mammalian cells. Gene Ther. 10:1791–1799. 2003. View Article : Google Scholar : PubMed/NCBI

16. 

Mayne LV, Jones T, Dean SW, Harcourt SA, Lowe JE, Priestley A, Steingrimsdottir H, Sykes H, Green HL and Lehmann R: SV40-transformed normal and DNA-repair-deficient human fibroblasts can be transfected with high frequency but retain only limited amounts of integrated DNA. Gene. 66:65–76. 1988. View Article : Google Scholar : PubMed/NCBI

17. 

Bartholomew C and Ihle JN: Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter. Mol Cell Biol. 11:1820–1828. 1991.PubMed/NCBI

18. 

Lazo PA, Lee JS and Tsichlis PN: Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi1 or Mlvi4 in rat T-cell lymphomas. Proc Natl Acad Sci USA. 87:170–173. 1990.

19. 

Bedigian HG, Johnson DA, Jenkins NA, Copeland NG and Evans R: Spontaneous and induced leukemias of myeloid origin in recombinant inbred BXH mice. J Virol. 51:586–594. 1984.PubMed/NCBI

20. 

Largaespada DL, Brannan CI, Jenkins NA and Copeland NG: Nf1 deficiency causes Ras-mediated granulocyte/macrophage stimulating factor hypersensitivity and chronic myeloid leukemia. Nat Genet. 12:137–143. 1996. View Article : Google Scholar

21. 

Blaydes SM, Kogan SC, Truong BH, Gilbert DJ, Jenkins NA, Copeland NG, Largaespada DA and Brannan CI: Retroviral integration at the Epi1 locus cooperates with the Nf1 gene loss in the progression to acute myeloid leukemia. J Virol. 75:9427–9434. 2001.PubMed/NCBI

22. 

Shimizu S, Suzukawa K, Kodera T, Nagasawa T, Abe T, Taniwaki M, Yagasaki F, Tanaka H, Fujisawa S, Johansson B, Ahlgren T, Yokota J and Morishita K: Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21). Genes Chromosomes Cancer. 27:229–238. 2000. View Article : Google Scholar : PubMed/NCBI

23. 

Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J and Morishita K: A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells. Blood. 96:3209–3214. 2000.PubMed/NCBI

24. 

Sakai I, Tamura T, Narumi H, Uchida N, Yakushijin Y, Hato T, Fujita S and Yasukawa M: Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21) (p36;q22). Genes Chromosomes Cancer. 44:265–270. 2005. View Article : Google Scholar : PubMed/NCBI

25. 

Nishikata I, Sasaki H, Iga M, Tateno Y, Imayoshi S, Asou N, Nakamura T and Morishita K: A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood. 102:3323–3332. 2003. View Article : Google Scholar : PubMed/NCBI

26. 

Xiao Z, Zhang M, Liu X, Zhang Y, Yang L and Hao Y: MEL1S, not MEL1, is overexpressed in myelodysplastic syndrome patients with t(1;3)(p36;q21). Leuk Res. 30:332–334. 2006. View Article : Google Scholar : PubMed/NCBI

27. 

Du Y, Jenkins NA and Copeland NG: Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells. Blood. 106:3932–3939. 2005. View Article : Google Scholar : PubMed/NCBI

28. 

Steidl U, Steidl C, Ebralidze A, Chapuy B, Han HJ, Will B, Rosenbauer F, Becker A, Wagner K, Koschmieder S, Kobayashi S, Costa DB, Schulz T, O’Brien KB, Verhaak RGW, Griesinger F and Tenen DG: A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia. J Clin Invest. 117:2611–2620. 2007. View Article : Google Scholar : PubMed/NCBI

29. 

Tenen DG: Disruption of differentiation in human cancer: AML shows the way. Nat Rev Cancer. 3:89–101. 2003. View Article : Google Scholar : PubMed/NCBI

30. 

Iwasaki H, Somoza C, Shigematsu H, Duprez EA, Iwasaki-Arai J, Mizuno S, Arinobu Y, Geary K, Zhang P, Dayaram T, Fenyus ML, Elf S, Chan S, Kastner P, Huettner CS, Murray R, Tenen DG and Akashi K: Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood. 106:1590–1600. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Haeri M, Li Y, Li Y, Li Q, Spaner DE and Ben-David Y: Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia. Int J Oncol 43: 169-176, 2013.
APA
Haeri, M., Li, Y., Li, Y., Li, Q., Spaner, D.E., & Ben-David, Y. (2013). Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia. International Journal of Oncology, 43, 169-176. https://doi.org/10.3892/ijo.2013.1943
MLA
Haeri, M., Li, Y., Li, Y., Li, Q., Spaner, D. E., Ben-David, Y."Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia". International Journal of Oncology 43.1 (2013): 169-176.
Chicago
Haeri, M., Li, Y., Li, Y., Li, Q., Spaner, D. E., Ben-David, Y."Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia". International Journal of Oncology 43, no. 1 (2013): 169-176. https://doi.org/10.3892/ijo.2013.1943
Copy and paste a formatted citation
x
Spandidos Publications style
Haeri M, Li Y, Li Y, Li Q, Spaner DE and Ben-David Y: Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia. Int J Oncol 43: 169-176, 2013.
APA
Haeri, M., Li, Y., Li, Y., Li, Q., Spaner, D.E., & Ben-David, Y. (2013). Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia. International Journal of Oncology, 43, 169-176. https://doi.org/10.3892/ijo.2013.1943
MLA
Haeri, M., Li, Y., Li, Y., Li, Q., Spaner, D. E., Ben-David, Y."Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia". International Journal of Oncology 43.1 (2013): 169-176.
Chicago
Haeri, M., Li, Y., Li, Y., Li, Q., Spaner, D. E., Ben-David, Y."Insertional activation of myb by F-MuLV in SCID mice induces myeloid leukemia". International Journal of Oncology 43, no. 1 (2013): 169-176. https://doi.org/10.3892/ijo.2013.1943
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