EXPRESSION OF HUMAN RECOMBINATION ACTIVATING GENES (RAG-1 AND RAG-2) IN LYMPHOMA

Two recently discovered genes, the recombination activating genes 1 an d 2 (RAG-1 and RAG-2), are necessary to perform variable (V), diversit y (D), and joining (J) recombination. They synergistically activate VD J recombination to generate immunocompetent lymphocytes. Disruption of either gene results in a maturation arrest at a very early B and T ce ll progenitor stage. Expression and downregulation of RAG's are closel y associated with interleukin 7, sIgM and TCR-CD3 complex, respectivel y. Assessment of RAG mRNA expression is a valuable marker in identifyi ng the genotypic maturation status of leukemias and lymphomas. Persist ent RAG expression in otherwise mature lymphoid proliferations may exp lain puzzling biological and clinical observations such as multiple re arrangements in lymphomas with a mature phenotype. Lack of RAG express ion in Hodgkin's disease with abundant Reed-Sternberg cells is consist ent with a mature phenotype of the latter. Availability of a anti-RAG- 1 monoclonal antibody in the near future will facilitate RAG analysis of lymphomas.