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Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma

Authors

  • S. Mathas
  • M. Janz
  • F. Hummel
  • M. Hummel
  • B. Wollert-Wulf
  • S. Lusatis
  • I. Anagnostopoulos
  • A. Lietz
  • M. Sigvardsson
  • F. Jundt
  • K. Joehrens
  • K. Bommert
  • H. Stein
  • B. Doerken

Journal

  • Nature Immunology

Citation

  • Nat Immunol 7 (2): 207-215

Abstract

  • B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell-determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.


DOI

doi:10.1038/ni1285