Correlation among nuclear localization of NuMA-RARα, deregulation of gene expression and leukemic phenotype of hCG-NuMA-RARα transgenic mice

Leuk Res. 2011 May;35(5):670-6. doi: 10.1016/j.leukres.2010.12.009. Epub 2011 Jan 21.

Abstract

Acute promyelocytic leukemia (APL) is a model system of aberrant transcription in cancer. We sought to elucidate the mechanism of action of the variant fusion NuMA-RARα in APL, using the hCG-NuMA-RARα transgenic model. We report that subcellular localization of NuMA-RARα in transgenic mice is dependent upon its protein expression and transgene dosage. Subcellular localization of the fusion is inversely correlated with extent of gene deregulation at the mRNA level for Cebpα, Cebpɛ and Pu.1. Finally, we report that phenotype onset is correlated with NuMA-RARα copy number; mice with higher copy number developing disease later than those with lower copy number.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • Chorionic Gonadotropin / genetics
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Disease Models, Animal
  • Gene Dosage
  • Gene Expression Regulation, Leukemic
  • Humans
  • Leukemia / genetics
  • Leukemia / metabolism
  • Leukemia / pathology*
  • Mice
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Phenotype
  • Protein Transport
  • Transgenes / genetics
  • U937 Cells

Substances

  • Chorionic Gonadotropin
  • NuMa-RARalpha protein, human
  • Oncogene Proteins, Fusion