Early B-cell factor-associated zinc-finger gene is a frequent target of retroviral integration in murine B-cell lymphomas

Søren Warming, Takeshi Suzuki, Terry P. Yamaguchi, Nancy A. Jenkins, Neal G. Copeland

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The early B-cell factor (EBF)-associated zinc-finger protein (EBFAZ) binds to and negatively regulates EBF, a basic helix-loop-helix transcription factor required for B-cell lineage commitment and development of the olfactory epithelium. It also binds to SMA- and MAD-related protein 1 (SMAD1) and SMAD4 in response to bone morphogenic protein 2 (BMP2) signaling. It is highly related to ecotropic viral integration site 3 (EVI3), a protein that, like EBFAZ, contains 30 Krüppel-like zinc-finger repeats. In previous studies, we showed that Evi3 is a frequent target of retroviral integration in AKXD27 B-cell lymphomas. Here, we show that EBFAZ is also a frequent target. Integrations at Ebfaz and Evi3 are mutually exclusive, suggesting that they function in the same tumor pathway. Lymphomas with integrations at Ebfaz or Evi3 express the pre-B-cell-specific marker immunoglobulin lambda chain 5, and contain immunoglobulin heavy-chain rearrangements, suggesting that they are blocked at an early B-cell stage. Unlike Evi3, which is expressed at low levels in normal B cells, or Ebfaz, which is not expressed in B cells, both genes are highly expressed following viral integration. Collectively, our results suggest that ectopic expression of Ebfaz can substitute for the upregulated expression of Evi3 in B-cell disease and highlight the importance of this gene family in hematopoietic cancer.

Original languageEnglish (US)
Pages (from-to)2727-2731
Number of pages5
JournalOncogene
Volume23
Issue number15
DOIs
StatePublished - Apr 8 2004

Keywords

  • B-cell lymphoma
  • EBFAZ
  • EVI3

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Early B-cell factor-associated zinc-finger gene is a frequent target of retroviral integration in murine B-cell lymphomas'. Together they form a unique fingerprint.

Cite this