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E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas

Academic Article
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Overview

authors

  • Bain, G.
  • Enel, I.
  • Maandag, E. C. R.
  • teRiele, H. P. J.
  • Voland, J. R.
  • Sharp, L. L.
  • Chun, Jerold
  • Huey, B.
  • Pinkel, D.
  • Murre, C.

publication date

  • 1997

journal

  • Molecular and Cellular Biology  Journal

abstract

  • The E2A gene products, E12 and E47, are critical for proper early B-cell development and commitment to the B-cell lineage. Here we reveal a new role for E2A in T-lymphocyte development. Loss of E2A activity results in a partial block at the earliest stage of T-lineage development. This early T-cell phenotype precedes the development of a T-cell lymphoma which occurs between 3 and 9 months of age. The thymomas are monoclonal and highly malignant and display a cell surface phenotype similar to that of immature thymocytes. In addition, the thymomas generally express high levels of c-myc. As assayed by comparative genomic hybridization, each of the tumor populations analyzed showed a nonrandom gain of chromosome 15, which contains the c-myc gene. Taken together, the data suggest that the E2A gene products play a role early in thymocyte development that is similar to their function in B-lineage determination. Furthermore, the lack of E2A results in development of T-cell malignancies, and we propose that E2A inactivation is a common feature of a wide variety of human T-cell proliferative disorders, including those involving the E2A heterodimeric partners tal-1 and lyl-1.

subject areas

  • Animals
  • Cell Differentiation
  • Cell Extracts
  • Cell Nucleus
  • Chromosome Aberrations
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Genes, myc
  • Lymphocyte Subsets
  • Lymphoma, T-Cell
  • Mice
  • Mice, Knockout
  • Mice, Nude
  • T-Lymphocytes
  • TCF Transcription Factors
  • Thymoma
  • Thymus Gland
  • Thymus Neoplasms
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
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Identity

PubMed Central ID

  • PMC232330

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.17.8.4782

PubMed ID

  • 9234734
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Additional Document Info

start page

  • 4782

end page

  • 4791

volume

  • 17

issue

  • 8

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