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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 411-416
Reed-Sternberg Cell Genome Expression Supports a B-Cell Lineage
Jeffrey Cossman,
Christina M. Annunziata,
Steven Barash,
Louis Staudt,
Patrick Dillon,
Wei-Wu He,
Paola Ricciardi-Castagnoli,
Craig A. Rosen, and
Kenneth C. Carter
From the Georgetown University Medical Center, Washington, DC; Human
Genome Sciences, Inc, Rockville, MD; the National Cancer Institute,
National Institutes of Health, Bethesda, MD; and the University of
Milano-Bicocca, Milan, Italy.
The malignant Reed-Sternberg cell of Hodgkin's disease, first
described a century ago, has resisted in-depth analysis due to its
extreme rarity in lymphomatous tissue. To directly study its
genome-wide gene expression, approximately 11,000,000 bases (27,518 cDNA sequences) of expressed gene sequence was determined from living
single Reed-Sternberg cells, Hodgkin's tissue, and cell lines. This
approach increased the number of genes known to be expressed in
Hodgkin's disease by 20-fold to 2,666 named genes. The data here
indicate that Reed-Sternberg cells from both nodular sclerosing and
lymphocyte predominant Hodgkin's disease were derived from an unusual
B-cell lineage based on a comparison of their gene expression to
approximately 40,000,000 bases (105 sequences) of expressed
gene sequence from germinal center B cells (GCB) and dendritic cells.
The data set of expressed genes, reported here and on the World Wide
Web, forms a basis to understand the genes responsible for Hodgkin's
disease and develop novel diagnostic markers and therapies. This study
of the rare Reed-Sternberg cell, concealed in its heterogenous cellular
context, also provides a formidable test case to advance the limit of
analysis of differential gene expression to the single disease cell.
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