The fusion partner specifies the oncogenic potential of NUP98 fusion proteins

Leuk Res. 2013 Dec;37(12):1668-73. doi: 10.1016/j.leukres.2013.09.013. Epub 2013 Sep 21.

Abstract

NUP98 is among the most promiscuously translocated genes in hematological diseases. Among the 28 known fusion partners, there are two categories: homeobox genes and non-homeobox genes. The homeobox fusion partners are well-studied in animal models, resulting in HoxA cluster overexpression and hematological disease. The non-homeobox fusion partners are less well studied. We created transgenic animal models for three NUP98 fusion genes (one homeobox, two non-homeobox), and show that in this system, the NUP98-homeobox fusion promotes self-renewal and aberrant gene expression to a significantly greater extent. We conclude that homeobox partners create more potent NUP98 fusion oncogenes than do non-homeobox partners.

Keywords: HOX; Homeobox; Leukemia; NUP98; Translocation.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured
  • Cytoskeletal Proteins / genetics
  • DNA Topoisomerases, Type I / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Homeodomain Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nuclear Pore Complex Proteins / genetics*
  • Oncogene Proteins, Fusion / physiology*
  • Translocation, Genetic / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Guanine Nucleotide Exchange Factors
  • Homeodomain Proteins
  • Nuclear Pore Complex Proteins
  • Oncogene Proteins, Fusion
  • nuclear pore complex protein 98
  • Kifap3 protein, mouse
  • DNA Topoisomerases, Type I