Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency.
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.
Yenson
Paul R
PR
Leukemia/Bone Marrow Transplantation Program of British Columbia, Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency, Vancouver, Canada.
Forrest
Donna
D
Schmiegelow
Kjell
K
Dalal
Bakul I
BI
D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine