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.

The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene

Abstract

Several tyrosine kinase genes are involved in chromosomal translocations in chronic myeloproliferative disorders, but there are still uncharacterized translocations in some cases. We report two such cases corresponding to atypical chronic myeloid leukaemia with a t(8;9)(p22;p24) translocation. By fluorescence in situ hybridisation (FISH) on the corresponding metaphases with a bacterial artificial chromosome probe encompassing the janus kinase 2 (JAK2) gene at 9p24, we observed a split for both patients, suggesting that this gene was rearranged. The locus at 8p22 contains different candidate genes including the pericentriolar material 1 gene (PCM1), already implicated in reciprocal translocations. The rearrangement of the PCM1 gene was demonstrated by FISH, for both patients. By RT–PCR, we confirmed the fusion of 3′ part of JAK2 with the 5′ part of PCM1. Sequence analysis of the chimeric PCM1-JAK2 mRNA suggests that the putative protein displays the coiled-coil domains of PCM1 and the tyrosine kinase domain of JAK2. This new translocation identifies JAK2 as a possible therapeutic target for compounds with antityrosine kinase activity.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2
Figure 3

References

  • Balczon R, Bao L and Zimmer WE . (1994). J. Cell Biol., 124, 783–793.

  • Balczon R, Simerly C, Takahashi D and Schatten G . (2002). Cell Motil. Cytoskeleton., 52, 183–192.

  • Barber DL and D'Andrea AD . (1994). Mol. Cell. Biol., 14, 6506–6514.

  • Baxter EJ, Hochhaus A, Bolufer P, Reiter A, Fernandez JM, Senent L, Cervera J, Moscardo F, Sanz MA and Cross NC . (2002). Hum. Mol. Genet., 11, 1391–1397.

  • Baxter EJ, Kulkarni S, Vizmanos JL, Jaju R, Martinelli G, Testoni N, Hughes G, Salamanchuk Z, Calasanz MJ, Lahortiga I, Pocock CF, Dang R, Fidler C, Wainscoat JS, Boultwood J and Cross NC . (2003). Br. J. Haematol., 120, 251–256.

  • Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN and Green AR . (2005). Lancet, 365, 1054–1061.

  • Bhattacharya N, Tripathi A, Dasgupta S, Sabbir MG, Roy A, Sengupta A, Roy B, Roychowdhury S and Panda CK . (2003). Indian J. Med. Res., 118, 77–85.

  • Carron C, Cormier F, Janin A, Lacronique V, Giovannini M, Daniel MT, Bernard O and Ghysdael J . (2000). Blood, 95, 3891–3899.

  • Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R and Gilliland DG . (2003). N. Engl. J. Med., 348, 1201–1214.

  • Corvi R, Berger N, Balczon R and Romeo G . (2000). Oncogene, 19, 4236–4242.

  • Dammermann A, Muller-Reichert T, Pelletier L, Habermann B, Desai A and Oegema K . (2004). Dev. Cell., 7, 815–829.

  • Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R and Talpaz M . (2001). N. Engl. J. Med., 344, 1038–1042.

  • Emi M, Fujiwara Y, Nakajima T, Tsuchiya E, Tsuda H, Hirohashi S, Maeda Y, Tsuruta K, Miyaki M and Nakamura Y . (1992). Cancer Res., 52, 5368–5372.

  • Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD and Fletcher JA . (2003). Science, 299, 708–710.

  • Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR and Grosveld G . (1983). Nature, 306, 239–242.

  • James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, Garcon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N and Vainchenker W . (2005). Nature, 434, 1144–1148.

  • Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J and Bernard OA . (1997). Science, 278, 1309–1312.

  • Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ and Gilliland DG . (2005). Cancer cell, 7, 387–397.

  • Nguyen MH, Ho JM, Beattie BK and Barber DL . (2001). J. Biol. Chem., 276, 32704–32713.

  • Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H and Marynen P . (1997). Blood, 90, 2535–2540.

  • Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A and Cross NC . (2005). Cancer Res., 65, 2662–2667.

  • Trempat P, Villalva C, Laurent G, Armstrong F, Delsol G, Dastugue N and Brousset P . (2003). Oncogene, 22, 5702–5706.

  • Valdembri D, Serini G, Vacca A, Ribatti D and Bussolino F . (2002). FASEB J., 16, 225–227.

Download references

Acknowledgements

We thank Dr Storlazzi, University of Milano, and Dr Max Chaffanet, INSERM U119, Marseille, for the generous gift of the BAC JAK2 (RP11-927H16) and PCM1 (RP11-484L21), respectively. Special thanks to Drs Fabienne Meggetto and Jean-Pierre Jaffrezou, INSERM U563 CPTP, Toulouse, France, for critical reading of the manuscript.

Grants: Cancéropole Grand Sud Ouest, Ligue contre le Cancer, Comités du Gers et de la Haute Garonne

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pierre Brousset.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bousquet, M., Quelen, C., De Mas, V. et al. The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. Oncogene 24, 7248–7252 (2005). https://doi.org/10.1038/sj.onc.1208850

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208850

Keywords

  • atypical chronic myeloid leukaemia
  • JAK2
  • PCM1

This article is cited by

Search

Quick links