Rearranging antigen-receptor genes in enriched reed-sternberg cell fractions of Hodgkin's disease

✍ Scribed by Jeffrey Cossman; James Sundeen; Michael Uppenkamp; Eileen Sussman; Larry Wahl; Robert Coupland; Edward Lipford; Mark Raffeld

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 774 KB
• Volume: 6
• Category: Article
• ISSN: 0278-0232
• DOI: 10.1002/hon.2900060303

✦ Synopsis

Molecular genetic analysis of rearranging antigen-receptor genes in non-Hodgkin's lymphomas has revealed the clonality and lineage in the majority of cases. In an analogous approach, we sought to apply gene rearrangement analysis to Hodgkin's disease to understand better the clonality and origin of this disorder. However, the putative neoplastic cell of Hodgkin's disease, the Reed-Stemberg cell and its variants, is extraordinarily rare in most cases of Hodgkin's disease. On the average, Reed-Stemberg cells and variants represent 0.1 per cent of total cell suspensions of nodular sclerosing Hodgkin's disease. As this frequency is below the minimum threshold of sensitivity of the Southern blot assay, we attempted to enrich for Reed-Sternberg cells before DNA extraction and analysis. Using either elutrition or Perm11 density gradient centrifugation, we were able to enrich the percentage of Reed-Sternberg cells and variants to above 1 percent in five cases of nodular sclerosing Hodkin's disease. In three of these cases, immunoglobulin gene rearrangements were identified, but no T cell receptor gene rearrangements were seen. No rearrangements were detected in unseparated cells or in the Reed-Sternberg cell-depleted fractions. In addition, the L428 Hodgkin's disease cell line was found to have one rearranged and one deleted heavy-chain gene, a rearranged K gene, a rearranged A gene, and a single rearranged B allele. No rearrangements of the T, gene were found in L428.

Taken together, these findings indicate that clonal cell populations are present in Hodgkin's disease and suggest the possibility of a clonally expanded ly4phoid cell in this disorder.