GENE-EXPRESSION BY SINGLE REED-STERNBERG CELLS - PATHWAYS OF APOPTOSIS AND ACTIVATION

Although Hodgkin's disease is highly responsive to treatments that cau se apoptosis, it remains resistant to the physiological mechanisms int ended to cause cell death. Presumably, the Reed-Sternberg cell defies endogenous apoptosis, persists, accumulates, and manifests the maligna nt disorder seen clinically. The Reed-Sternberg cell expresses several members of the tumor necrosis factor receptor superfamily. This famil y of receptors is involved in both activation and proliferation of cel ls, as well as either protection from or initiation of apoptosis in ce lls expressing these surface proteins. Signals from these receptors af fect transcription. We reasoned that the activation state and resistan ce to apoptosis of Reed-Sternberg cells might be attributable to dysre gulation of genes controling these processes. To determine gene expres sion by Reed-Sternberg cells, we developed a method of micromanipulati on, global reverse transcription, and the reverse transcription-polyme rase chain reaction and applied it to 51 single Reed-Sternberg cells a nd their variants from six cases of Hodgkin's disease. This report ana lyzes the gene expression of bcl-xs, bcl-xl, bax-alpha, bax-beta, fadd , fas, fas ligand (fas L), ice, TNF-alpha, TNF-beta, TNFR1, TNFR2, TRA F1, TRAF2, TRAF3, clAP2, and tradd at the level of mRNA in the single Reed-Sternberg cells and their variants. The findings here suggest a m olecular mechanism for the activated state and in vivo survival occurr ing in untreated Reed-Sternberg cells of Hodgkin's disease. (C) 1998 b y The American Society of Hematology.