title: Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Azathioprine (AZA) metabolism largely parallels the endogenous purine pathways. To date, thiopurine methyltransferase (TPMT) deficiency has been reported as a cause of AZA-related bone marrow toxicity in 1 patient with rheumatoid arthritis (RA). We therefore studied purine enzyme activities in 3 patients with RA who experienced AZA-related bone marrow toxicity.
  
  
  METHODS
  Lymphocyte activity of purine nucleoside phosphorylase and 5'-nucleotidase (5NT) and erythrocyte activity of TPMT, key enzymes in thiopurine catabolism, were measured in 3 RA patients who had experienced AZA-related bone marrow toxicity and in 16 RA patients without signs of toxicity despite at least 6 months of treatment with AZA.
  
  
  RESULTS
  Two patients with AZA-related bone marrow toxicity were found to have a TPMT deficiency, 1 partial and 1 total. In the third patient, 5NT activity was found to be well below the lowest level observed in the control subjects.
  
  
  CONCLUSIONS
  All 3 patients with severe AZA-related bone marrow toxicity had abnormal purine enzyme activities. Deficiency of purine enzymes, including TPMT and 5NT, may be a cause of AZA-related bone marrow toxicity in patients with RA.
authors: Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
authors: P J
authors: PJ
authors: Kerstens
authors: J N
authors: JN
authors: Stolk
authors: R A
authors: RA
authors: De Abreu
authors: L H
authors: LH
authors: Lambooy
authors: L B
authors: LB
authors: van de Putte
authors: A A
authors: AA
authors: Boerbooms
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology*; D001379:Azathioprine / Q000009:adverse effects* / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D008875:Middle Aged; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase; D015720:5'-Nucleotidase; D001379:Azathioprine