Single-cell analysis of Hodgkin and Reed-Sternberg cells: Molecular heterogeneity of gene expression and p53 mutations

L. H. Trumper, G. Brady, A. Bagg, D. Gray, S. L. Loke, H. Griesser, R. Wagman, R. Braziel, R. D. Gascoyne, S. Vicini, N. N. Iscove, J. Cossman, T. W. Mak

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Abstract

We have used a single-cell based polymerase chain reaction (PCR) amplification technique to examine the gene expression pattern in single Hodgkin's and Reed-Sternberg (H and RS) cells from seven patients with Hodgkin's disease. Single cells were isolated from lymph nodes obtained at diagnosis (5 of 7 patients) or in first or second relapse (2 of 7 patients). Gene expression was examined by hybridization to a panel of 22 cDNA probes. Forty-nine H and RS cells (and 23 CD3+ or CD20+ lymphocytes as controls) from four patients with nodular sclerosing Hodgkin's disease (HD) and one patient each with lymphocyte predominant and mixed-cellularity HD were successfully analyzed by PCR. This analysis provides evidence that single H and RS cells can coexpress genes characteristic of several hematopoietic lineages (monocytes and lymphocytes). Genes characteristic of activated lymphoid cells are expressed in most H and RS cells. Heterogeneity of expression for certain genes between different cases was found and may eventually define molecular subgroups of HD. These findings indicate that H and RS cells of HD resemble activated hematopoietic cells. Phenotypically similar cells from different cases exhibit characteristic molecular differences. In one patient, 5 of 7 single RS cells showed identical p53 cDNA mutations at codon 246 on specific reverse transcriptase [RT]-PCR and sequencing of exons 5 through 8. The novel experimental approach may provide a valuable tool for understanding the molecular events in newly diagnosed Hodgkin's disease and progression of the disease.

Original languageEnglish (US)
Pages (from-to)3097-3115
Number of pages19
JournalBlood
Volume81
Issue number11
StatePublished - Jan 1 1993

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Trumper, L. H., Brady, G., Bagg, A., Gray, D., Loke, S. L., Griesser, H., Wagman, R., Braziel, R., Gascoyne, R. D., Vicini, S., Iscove, N. N., Cossman, J., & Mak, T. W. (1993). Single-cell analysis of Hodgkin and Reed-Sternberg cells: Molecular heterogeneity of gene expression and p53 mutations. Blood, 81(11), 3097-3115.