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