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Cell differentiation and altered IMP dehydrogenase expression induced in human T-lymphoblastoid leukemia cells by mycophenolic acid and tiazofurin

Journal Article · · Experimental Cell Research; (United States)
The IMP dehydrogenase inhibitors mycophenolic acid (MPA) and tiazofurin (TZ) induce a time- and dose-dependent inhibition of cell growth, as well as differentiation in T-lymphoid CEM-2 leukemia cells. The differentiated cells have acquired a suppressor/cytotoxic T-lymphocyte phenotype characterized by reactivity with maturation-specific monoclonal antibodies. Coadministration of guanosine and hypoxanthine reduces the growth inhibition and diminishes the induction of differentiation by either MPA or TZ. No such reduction was observed for differentiation induced by phorbol 12-myristate 13-acetate (PMA). The lack of a consistent pattern of IMPDH expression in CEM-2 cells treated with IMPDH inhibitors or PMA indicates that no general association exists between the induction of cell differentiation and the expression of IMPDH. Nevertheless, the results indicating the IMPDH inhibitors can induce differentiation in CEM-2 cells suggest that this treatment may provide a useful approach to circumvent the differentiation block in some tumor cells.
DOE Contract Number:
W-31109-ENG-38
OSTI ID:
5378006
Journal Information:
Experimental Cell Research; (United States), Journal Name: Experimental Cell Research; (United States) Vol. 187:1; ISSN ECREA; ISSN 0014-4827
Country of Publication:
United States
Language:
English