1. ¹Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA
2. ²University of Florida Shands Cancer Center, Gainesville, FL, USA

Correspondence: Dr V Prima, Department of Pediatric Hematology/Oncology, University of Florida College of Medicine, PO Box 103633, Gainesville, FL 32610-3633, USA. E-mail: vprima@ufl.edu

Received 24 July 2007; Revised 27 August 2007; Accepted 28 August 2007; Published online 27 September 2007.

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.