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

Leukemia. 2007 Dec;21(12):2470-5. doi: 10.1038/sj.leu.2404962. Epub 2007 Sep 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Adhesion
  • Cell Shape
  • Cell Transformation, Neoplastic / genetics
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 1 / ultrastructure
  • Chromosomes, Human, Pair 19 / genetics
  • Chromosomes, Human, Pair 19 / ultrastructure
  • Culture Media, Serum-Free / pharmacology
  • Humans
  • MADS Domain Proteins / genetics*
  • MEF2 Transcription Factors
  • Mice
  • Myogenic Regulatory Factors / genetics*
  • NIH 3T3 Cells
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / physiology*
  • RNA-Binding Proteins / genetics*
  • Recombinant Fusion Proteins / physiology
  • Transduction, Genetic
  • Translocation, Genetic
  • Tumor Stem Cell Assay

Substances

  • Culture Media, Serum-Free
  • DAZAP1 protein, human
  • DAZAP1-MEF2D fusion protein, human
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2D protein, human
  • MEF2D-DAZAP1 fusion protein, human
  • Myogenic Regulatory Factors
  • Oncogene Proteins, Fusion
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins