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Cytogenetics and Molecular Genetics

Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia

Leukemia volume 21, pages 2470–2475 (2007)Cite this article

Abstract

A variant t(1;19)(q23;p13.3) translocation creates reciprocal DAZAP1/MEF2D and MEF2D/DAZAP1 fusion genes that are expressed in acute lymphoblastic leukemia. We used retroviral gene transfer to ectopically express wild-type and chimeric DAZAP1 and MEF2D fusion proteins in NIH 3T3 cells. In soft agar assays, each of the fusion proteins transformed 3T3 cells with a 20-fold increase in colony formation as compared to empty vector or native MEF2D or DAZAP1 proteins. Co-expression of both DAZAP1/MEF2D and MEF2D/DAZAP1 led to a threefold increase in colony formation as compared to either fusion protein alone. Expression of wild-type DAZAP1, MEF2D or DAZAP1/MEF2D allowed 3T3 cells to proliferate under low serum (0.5%) conditions and suppressed apoptosis. In contrast, MEF2D/DAZAP1 expression did not facilitate proliferation in low serum and led to a modest increase in apoptosis. Both MEF2D/DAZAP1 and DAZAP1/MEF2D have oncogenic properties, and co-expression of both fusion proteins is synergistic.

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Acknowledgements

We thank Drs Brad Fletcher and Kishalay Hoare, University of Florida, for providing the packaging and target cell lines and valuable technical advice. This work was supported by a grant from the Pediatric Cancer Foundation to SPH.

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  1. Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA

    V Prima & S P Hunger

  2. University of Florida Shands Cancer Center, Gainesville, FL, USA

    V Prima & S P Hunger

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Correspondence to V Prima.

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Prima, V., Hunger, S. Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia. Leukemia 21, 2470–2475 (2007). https://doi.org/10.1038/sj.leu.2404962

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