Proliferation-linked Regulation of Type II IMP Dehydrogenase Gene in Human Normal Lymphocytes and HL-60 Leukemic Cells1

Human IMP dehydrogenase (IMPDH; EC 1.1.1.205) was recently found to consist of two molecular species (types I and II) with high expression of type II isozyme in leukemic cells. Here we report that the low level of type II inK.NA in normal lymphocytes was up-regulated by phytohemagglutinin stimulation (3.2-fold) and Epstein-Barr viral trans formation (5.7-fold). The type II mRNA expression in quiescent HL-60 cells was also elevated 2.8-fold by serum stimulation. Conversely the enhanced level of type II IMPDH mRNA in HL-60 cells was downregulated to less than 5% along with differentiation induced by retinole acid (l UM).phorbol-12-myristate-13-acetate (33 n\i), or dimethyl sulfoxide (1.25%) independent of end-stage phenotype. By contrast, type I IMPDH mRNA was expressed constitutively in the various states of proliferation and differentiation. The type II IMPDH stringently linked with cell proliferation should be a crucial target for antileukemic and immunosuppressive chemotherapy.