Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency

Am J Hematol. 2008 Jan;83(1):80-3. doi: 10.1002/ajh.21014.


Immunosuppressive thiopurines like azathioprine, 6-mercaptopurine, and thioguanine are commonly used in inflammatory and neoplastic disorders. A subset of these patients are genetically slow metabolizers due to point-mutations in enzyme thiopurine S-methyltransferase (TPMT), and are at a higher risk of hematologic toxicity and leukemogenesis. We present such a patient who was a slow metabolizer for azathioprine, and developed a rapidly lethal form acute myeloid leukemia after relatively low dose exposure to the drug. There was prominent hemophagocytic activity in the bone marrow, and cytogenetic analysis showed a complex karyotype with monosomy 7, but no involvement of chromosome 8.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Azathioprine / adverse effects*
  • Azathioprine / therapeutic use*
  • Bone Marrow / pathology
  • Crohn Disease / complications
  • Crohn Disease / drug therapy*
  • Female
  • Genotype
  • Humans
  • Leukemia, Myeloid, Acute / chemically induced
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / pathology*
  • Methyltransferases / deficiency*
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*


  • Methyltransferases
  • thiopurine methyltransferase
  • Azathioprine