INTERFERON-ALPHA-2B DOWN-REGULATION OF ONCOGENES H-RAS, C-RAF-2, C-KIT, C-MYC, C-MYB AND C-FOS IN ESKOL, A HAIRY-CELL LEUKEMIC LINE, RESULTS IN TEMPORAL PERTURBATION OF SIGNAL-TRANSDUCTION CASCADE

ESKOL, a B-lymphoblastoid cell line consisting of late differentiated cells, resembles hairy cell leukemia (HCL). It is pseudodiploid with a deleted 7q and an unbalanced translocation between chromosomes 4 and 6. It was screened by Northern hybridization for oncogenes, including H-ras, c-raf-2 (c-raf1 p1), c-kit, c-myc, c-myb, c-fos, Fim-1, c-jun, ski, and c-mos, which are believed to contribute to B-cell differentia tion and maturation. Interferon-alpha-2b (IFN) downregulates the expre ssion of H-ras, c-raf-2, c-kit, c-myc, c-myb, c-fos, as determined by Northern hybridization of RNA isolated from cells harvested at time po ints during a 30 h time course. Downregulation of oncogenes H-ras, c-r af-a, c-kit, whose proteins are associated with cell surfaces or are c ytosolar transducers, occurs before those oncogenes c-myc, c-myb, and c-fos, whose products are DNA binding proteins. This suggests a tempor al perturbation of signal transduction by IFN. No change in oncogene e xpression occurred in non-treated cells nor were these oncogenes expre ssed in the non-transformed B-lymphoblast cell line, Wil-2, under the same treatment regimen. The basis for the IFN perturbation is not unde rstood; yet the role of these oncogenes as signal transducers in diffe rentiation and proliferation of human hematopoietic progenitors is unf olding, and ESKOL is an excellent system in which to study this phenom enon.