[Proliferative signal transmission mediated by EpoR in leukemic cell lines].

OBJECTIVE: To investigate the expression of erythropoietin receptor (EpoR) in leukemic cell lines and to clarify the mechanism of proliferative signal transmission in the leukemic cell line KOCL-33 mediated by EpoR. METHODS: Biotinylated Epo and flow cytometry were used for EpoR expression, (3)H-TdR incorporation for cell proliferation, immunoprecipitation and Western blot analysis for the tyrosine phosphorylation of signal transmission proteins. RESULTS: (1) All the cell lines tested expressed EpoR except for T-lymphoid cell lines. The positivity rates ranged from 18% to 99% with an average of 52%, and was no difference among T, B and non-lymphoid cells. (2) The cell proliferation was significantly enhanced in response to Epo in 7 of 9 cell lines tested. The stimulating effects of Epo did not correlate with the densities of EpoR expressed on the cells. (3) The proliferation of KOCL-33 cells was significantly enhanced in response to Epo. Dimerization and tyrosine phosphorylation of EpoR and tyrosine phosphorylation of JAK2 occurred in 1 min and tyrosine phosphorylation of STAT5 in 5 minutes after Epo stimulation. CONCLUSION: (1) There was EpoR expression in leukemic cell lines. (2) The cell proliferation could be stimulated by Epo in some leukemic cell lines. The stimulating effect of Epo did not correlate with the densities of EpoR expressed on the cells. (3) Dimerization and tyrosine phosphorylation of EpoR occurred, and JAK2, STAT5 involved in the proliferative signal transmission in KOCL-33 cells mediated by EpoR.