Abstract
PAX5, a master regulator of B-cell development, was recently shown to be involved in several leukemia-associated rearrangements, which result in fusion genes encoding chimeric proteins that antagonize PAX5 transcriptional activity. In a population-based fluorescence in situ hybridization screening study of 446 childhood acute lymphoblastic leukemia (ALL) patients, we now show that PAX5 rearrangements occur at an incidence of about 2.5% of B-cell precursor ALL. Identification of several novel PAX5 partner genes, including POM121, BRD1, DACH1, HIPK1 and JAK2 brings the number of distinct PAX5 in-frame fusions to at least 12. Our data show that these not only comprise transcription factors but also structural proteins and genes involved in signal transduction, which at least in part have not been implicated in tumorigenesis.
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Acknowledgements
This study was supported by a grant of the Austrian Ministry of Science and Research (GEN-AU II, GZ 200.136/1-VI/1/2005) (to SS) and the St Anna Kinderkrebsforschung. We thank Meinrad Busslinger (IMP, Vienna, Austria) for kindly providing the PAX5 cosmid probes and Tilman Johannes (MetaSystems, Altlussheim, Germany) for assistance with the Metafer4-Metacyte system. We thank all those people, who perform the routine diagnostic work-up and consistently provide the basis for our research. Further, we are indebted to Dasa Janousek for the efficient clinical data management and analysis.
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Nebral, K., Denk, D., Attarbaschi, A. et al. Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia 23, 134–143 (2009). https://doi.org/10.1038/leu.2008.306
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DOI: https://doi.org/10.1038/leu.2008.306
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