Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23)

Oncogene volume 25, pages 6147–6152 (2006)Cite this article

Abstract

We have identified a new mixed lineage leukemia (MLL) gene fusion partner in a patient with treatment-related acute myeloid leukemia (AML) presenting a t(2;11)(q37;q23) as the only cytogenetic abnormality. Fluorescence in situ hybridization demonstrated a rearrangement of the MLL gene and molecular genetic analyses identified a septin family gene, SEPT2, located on chromosome 2q37, as the fusion partner of MLL. RNA and DNA analyses showed the existence of an in-frame fusion of MLL exon 7 with SEPT2 exon 3, with the genomic breakpoints located in intron 7 and 2 of MLL and SEPT2, respectively. Search for DNA sequence motifs revealed the existence of two sequences with 94.4% homology with the topoisomerase II consensus cleavage site in MLL intron 7 and SEPT2 intron 2. SEPT2 is the fifth septin family gene fused with MLL, making this gene family the most frequently involved in MLL-related AML (about 10% of all known fusion partners). The protein encoded by SEPT2 is highly homologous to septins 1, 4 and 5 and is involved in the coordination of several key steps of mitosis. Further studies are warranted to understand why the septin protein family is particularly involved in the pathogenesis of MLL-associated leukemia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Abeysinghe SS, Chuzhanova N, Krawczak M, Ball EV, Cooper DN . (2003). Hum Mutat 22: 229–244.

  • Berger R, Flandrin G, Bernheim A, Le Coniat M, Vecchione D, Pacot A et al. (1987). Cancer Genet Cytogenet 29: 9–21.

  • Borkhardt A, Bojesen S, Haas OA, Fuchs U, Bartelheimer D, Loncarevic IF et al. (2000). Proc Natl Acad Sci USA 97: 9168–9173.

  • Chinwalla V, Chien A, Odero M, Neilly MB, Zeleznik-Le NJ, Rowley JD . (2003). Oncogene 22: 1400–1410.

  • Chuzhanova N, Abeysinghe SS, Krawczak M, Cooper DN . (2003). Hum Mutat 22: 245–251.

  • Daser A, Rabbitts TH . (2005). Semin Cancer Biol 15: 175–188.

  • DeLozier-Blanchet CD, Cabrol C, Werner-Favre C, Beris P, Engel E . (1985). Cancer Genet Cytogenet 16: 95–102.

  • Fischer K, Frohling S, Scherer SW, McAllister Brown J, Scholl C, Stilgenbauer S et al. (1997). Blood 89: 2036–2041.

  • Fuchs U, Rehkamp G, Haas OA, Slany R, Konig M, Bojesen S et al. (2001). Proc Natl Acad Sci USA 98: 8756–8761.

  • Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR . (2005). J Pathol 205: 154–171.

  • Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G et al. (1992). Cell 71: 701–708.

  • Hall PA, Russell SE . (2004). J Pathol 204: 489–505.

  • Harrison CJ, Cuneo A, Clark R, Johansson B, Lafage-Pochitaloff M, Mugneret F et al. (1998). Leukemia 12: 811–822.

  • Hayette S, Tigaud I, Vanier A, Martel S, Corbo L, Charrin C et al. (2000). Oncogene 19: 4446–4450.

  • Huret JL . (2005). Atlas of Genetics and Cytogenetics in Oncology and Haematology http://www.infobiogen.fr/services/chromcancer/Genes/MLL.html.

  • Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M et al. (1997). Blood 90: 4699–4704.

  • ISCN (1995). An International System for Human Cytogenetic Nomenclature. Karger: Basel.

  • Kinoshita M, Kumar S, Mizoguchi A, Ide C, Kinoshita A, Haraguchi T et al. (1997). Genes Dev 11: 1535–1547.

  • Kojima K, Sakai I, Hasegawa A, Niiya H, Azuma T, Matsuo Y et al. (2004). Leukemia 18: 998–1005.

  • Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS et al. (2000). Proc Natl Acad Sci USA 97: 2145–2150.

  • Li ZY, Liu DP, Liang CC . (2005). Leukemia 19: 183–190.

  • Marosi C, Koller U, Koller-Weber E, Schwarzinger I, Schneider B, Jager U et al. (1992). Cancer Genet Cytogenet 61: 14–25.

  • Megonigal MD, Rappaport EF, Jones DH, Williams TM, Lovett BD, Kelly KM et al. (1998). Proc Natl Acad Sci USA 95: 6413–6418.

  • Milne TA, Briggs SD, Brock HW, Martin ME, Gibbs D, Allis CD et al. (2002). Mol Cell 10: 1107–1117.

  • Nakamura T, Mori T, Tada S, Krajewski W, Rozovskaia T, Wassell R et al. (2002). Mol Cell 10: 1119–1128.

  • Ono R, Nakajima H, Ozaki K, Kumagai H, Kawashima T, Taki T et al. (2005). J Clin Invest 115: 919–929.

  • Ono R, Taki T, Taketani T, Kawaguchi H, Taniwaki M, Okamura T et al. (2002). Cancer Res 62: 333–337.

  • Osaka M, Rowley JD, Zeleznik-Le NJ . (1999). Proc Natl Acad Sci USA 96: 6428–6433.

  • Poirel H, Rack K, Delabesse E, Radford-Weiss I, Troussard X, Debert C et al. (1996). Blood 87: 2496–2505.

  • Popovic R, Zeleznik-Le NJ . (2005). J Cell Biochem 95: 234–242.

  • Prasad R, Leshkowitz D, Gu Y, Alder H, Nakamura T, Saito H et al. (1994). Proc Natl Acad Sci USA 91: 8107–8111.

  • Pui CH, Relling MV . (2000). Br J Haematol 109: 13–23.

  • Rasmussen SW . (2004). SEQ Tools Version 8.2 – Build 101 http://www.seqtools.dk.

  • Rudiger NS, Gregersen N, Kielland-Brandt MC . (1995). Nucleic Acids Res 23: 256–260.

  • Russell SE, Hall PA . (2005). Br J Cancer 93: 499–503.

  • Satake N, Maseki N, Nishiyama M, Kobayashi H, Sakurai M, Inaba H et al. (1999). Leukemia 13: 1013–1017.

  • Savage PD, Shapiro M, Langdon WY, Geurts van Kessel AD, Seuanez HN, Akao Y et al. (1991). Cytogenet Cell Genet 56: 112–115.

  • Slany RK . (2005). Hematol Oncol 23: 1–9.

  • Smit AFA, Hubley R, Green P . (2004). RepeatMasker Open-3.0 http://www.repeatmasker.org.

  • So CW, Caldas C, Liu MM, Chen SJ, Huang QH, Gu LJ et al. (1997). Proc Natl Acad Sci USA 94: 2563–2568.

  • Sobulo OM, Borrow J, Tomek R, Reshmi S, Harden A, Schlegelberger B et al. (1997). Proc Natl Acad Sci USA 94: 8732–8737.

  • Spiliotis ET, Kinoshita M, Nelson WJ . (2005). Science 307: 1781–1785.

  • Strehl S, Borkhardt A, Slany R, Fuchs UE, Konig M, Haas OA . (2003). Oncogene 22: 157–160.

  • Surka MC, Tsang CW, Trimble WS . (2002). Mol Biol Cell 13: 353235–353245.

  • Taki T, Kano H, Taniwaki M, Sako M, Yanagisawa M, Hayashi Y . (1999b). Proc Natl Acad Sci USA 96: 14535–14540.

  • Taki T, Ohnishi H, Shinohara K, Sako M, Bessho F, Yanagisawa M et al. (1999a). Cancer Res 59: 4261–4265.

  • Taki T, Sako M, Tsuchida M, Hayashi Y . (1997). Blood 89: 3945–3950.

  • Tkachuk DC, Kohler S, Cleary ML . (1992). Cell 71: 691–700.

  • von Bergh AR, Wijers PM, Groot AJ, van Zelderen-Bhola S, Falkenburg JH, Kluin PM et al. (2004). Genes Chromosomes Cancer 39: 324–334.

  • Winick NJ, McKenna RW, Shuster JJ, Schneider NR, Borowitz MJ, Bowman WP et al. (1993). J Clin Oncol 11: 209–217.

  • Yamamoto K, Seto M, Iida S, Komatsu H, Kamada N, Kojima S et al. (1994). Blood 83: 2912–2921.

Download references

Acknowledgements

This research was supported by Liga Portuguesa Contra o Cancro – Núcleo Regional do Norte.

Author information

Authors and Affiliations

  1. Department of Genetics, Portuguese Oncology Institute, Porto, Portugal

    N Cerveira, C Correia, S Bizarro, C Pinto, S Lisboa & M R Teixeira

  2. Department of Onco-Hematology, Portuguese Oncology Institute, Porto, Portugal

    J M Mariz & M Marques

Authors
  1. N Cerveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Correia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Bizarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Lisboa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J M Mariz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M R Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M R Teixeira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cerveira, N., Correia, C., Bizarro, S. et al. SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23). Oncogene 25, 6147–6152 (2006). https://doi.org/10.1038/sj.onc.1209626

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209626

Keywords

This article is cited by

Search

Advanced search

Quick links