title: A possible explanation for anemia in patients treated with mycophenolic acid.
abstract: BACKGROUND
  Clinical studies suggest that the immunosuppressant mycophenolate mofetil is associated with anemia. However, the mechanism for this is not known. Here, we studied the effect of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, on erythropoiesis in vitro.
  
  
  METHODS
  Both UT-7 cells and primary murine bone marrow cells were studied. Cells were initially treated with erythropoietin and MPA and proliferation and caspase-3 assays were performed. The effect of guanosine-5'-triphosphate, guanosine, and caspase inhibitors was also investigated.
  
  
  RESULTS
  MPA was found to decrease the proliferation of UT-7 cells and erythropoiesis in murine bone marrow cells. This inhibition was associated with an increase in caspase-3 activity in the UT-7 cells. Inhibition was reversed in UT-7 cells and in murine bone marrow by guanosine, but not by caspase inhibitors. The apoptosis induced by MPA was also reversed by guanosine. UT-7 cells treated with MPA showed a decreased inosine-5'-monophosphate dehydrogenase activity.
  
  
  CONCLUSIONS
  These results suggest that MPA inhibits inosine-5'-monophosphate dehydrogenase activity in erythroid cells and that this is a likely mechanism of action of anemia in MPA-treated patients.
authors.affiliation: William Harvey Research Institute, Queen Mary, University of London, London, UK. teeps_tp@yahoo.com
authors.forename: Taryn
authors.initials: T
authors.lastname: Pile
authors.forename: Julius
authors.initials: J
authors.lastname: Kieswich
authors.forename: Steven
authors.initials: S
authors.lastname: Harwood
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Yaqoob
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D051379:Mice; D009173:Mycophenolic Acid / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000378:metabolism; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D004921:Erythropoietin; D007168:IMP Dehydrogenase; D053148:Caspase 3; D009173:Mycophenolic Acid