Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease

Blood. 2002 Apr 15;99(8):3060-2. doi: 10.1182/blood.v99.8.3060.

Abstract

Immunoglobulin transcription is impaired in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD). We recently demonstrated that defective immunoglobulin promoter transcription correlates with the down-regulation of the B-cell transcription factors Oct2 and BOB.1/OBF.1. These results prompted us to investigate whether immunoglobulin enhancer activity is also impaired in HRS cells and whether as yet unidentified factors could be necessary for immunoglobulin enhancer activity in HRS cells of cHD. Here we analyzed 30 cases of cHD for expression of the Ets family member PU.1 that is known to collaborate with multiple transcription factors and to regulate expression of immunoglobulin genes. We show that PU.1 is not expressed in primary and cultured HRS cells. Reintroduction of PU.1 and Oct2 in cultured HRS cells restored the activity of cotransduced immunoglobulin enhancer constructs. Our study identifies PU.1 deficiency as a recurrent defect in HRS cells that might contribute to their impairment of immunoglobulin transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / pharmacology
  • Down-Regulation
  • Genes, Immunoglobulin / drug effects
  • Hodgkin Disease / immunology
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology*
  • Humans
  • Immunoglobulins / drug effects
  • Immunoglobulins / genetics*
  • Lymph Nodes / pathology
  • Octamer Transcription Factor-2
  • Promoter Regions, Genetic / drug effects
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / pharmacology
  • Reed-Sternberg Cells / immunology
  • Reed-Sternberg Cells / metabolism*
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics
  • Trans-Activators / pharmacology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / pharmacology
  • Transcription, Genetic / drug effects
  • Transfection
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • Immunoglobulins
  • Octamer Transcription Factor-2
  • POU2AF1 protein, human
  • POU2F2 protein, human
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • proto-oncogene protein Spi-1