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Related Experiment Videos

E mu-BRD2 transgenic mice develop B-cell lymphoma and leukemia.

Rebecca J Greenwald1, Joseph R Tumang, Anupama Sinha

  • 1Department of Pathology, Immunology Research Division, Brigham and Women's Hospital, Harvard Medcial School, Boston, MA, USA.

Blood
|October 18, 2003
PubMed
Summary

Overexpression of bromodomain-containing 2 (Brd2) in mice causes B-cell lymphoma and leukemia. Brd2

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Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Bromodomain-containing 2 (Brd2) is a nuclear protein kinase.
  • Brd2 is structurally similar to TAF(II)250 and Drosophila female sterile homeotic.
  • Its role in lymphomagenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of Brd2 in B-cell lymphomagenesis.
  • To establish a transgenic mouse model for Brd2-induced lymphoma.

Main Methods:

  • Lymphoid-restricted overexpression of Brd2 in transgenic mice.
  • Transplantation of lymphoma cells.
  • Analysis of gene expression and cell surface markers.
  • Comparison of wild-type and kinase-null Brd2 transgenes.

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Main Results:

  • Transgenic mice developed B-cell lymphoma and leukemia.
  • Lymphoma cells exhibited B-1 cell features (CD5+, surface IgM+).
  • Lymphoma was monoclonal and phenotypically stable.
  • Both wild-type and kinase-null Brd2 induced lymphomagenesis.

Conclusions:

  • Constitutive Brd2 expression drives B-cell lymphomagenesis.
  • Brd2-mediated recruitment of transcription factors to the cyclin A promoter is key.
  • This is the first transgenic model for constitutive expression of a multi-bromodomain protein.