Gene expression by single Reed-Sternberg cells: Pathways of apoptosis and activation

Christina Messineo, M. Hunter Jamerson, Eileen Hunter, Rita Braziel, Adam Bagg, Steven G. Irving, Jeffrey Cossman

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Although Hodgkin's disease is highly responsive to treatments that cause apoptosis, it remains resistant to the physiological mechanisms intended to cause call death. Presumably, the Reed-Sternberg call defies endogenous apoptosis, persists, accumulates, and manifests the malignant disorder seen clinically. The Reed-Sternberg cell expresses several members of the tumor necrosis factor receptor superfamily. This family of receptors is involved in both activation and proliferation of cells, as well as either protection from or initiation of apoptosis in calls expressing these surface proteins. Signals from these receptors affect transcription. We reasoned that the activation state and resistance to apoptosis of Reed-Sternberg calls might be attributable to dysregulation of genes controling these processes. To determine gene expression by Reed-Sternberg calls, we developed a method of micromanipulation, global reverse transcription, and the reverse transcription-polymerase chain reaction and applied it to 51 single Reed- Sternberg cells and their variants from six cases of Hodgkin's disease. This report analyzes the gene expression of bcl-xs, bcl-xl, bax-α, bax-β, fadd, fas, fas ligand (fas L), ice, TNF-α, TNF-β, TNFR1, TNFR2, TRAF1, TRAF2, TRAF3, cIAP2, and tradd at the level of mRNA in the single Reed-Sternberg cells and their variants. The findings here suggest a molecular mechanism for the activated state and in vivo survival occurring in untreated Reed- Sternberg calls of Hodgkin's disease.

Original languageEnglish (US)
Pages (from-to)2443-2451
Number of pages9
JournalBlood
Volume91
Issue number7
DOIs
StatePublished - Apr 1 1998

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Messineo, C., Jamerson, M. H., Hunter, E., Braziel, R., Bagg, A., Irving, S. G., & Cossman, J. (1998). Gene expression by single Reed-Sternberg cells: Pathways of apoptosis and activation. Blood, 91(7), 2443-2451. https://doi.org/10.1182/blood.v91.7.2443