TPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group

Pediatr Blood Cancer. 2014 Nov;61(11):2086-8. doi: 10.1002/pbc.25057. Epub 2014 Apr 16.

Abstract

Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well as by MTHFR genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was not associated with SOS risk. These suggest that germline genetic variation in TPMT and MTHFR do not significantly alter SOS risk in patients exposed to thioguanine.

Keywords: MTHFR; SOS; TPMT; acute lymphoblastic leukemia; thioguanine; toxicity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects*
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Hepatic Veno-Occlusive Disease / chemically induced
  • Hepatic Veno-Occlusive Disease / genetics*
  • Humans
  • Infant
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methyltransferases / genetics*
  • Polymorphism, Single Nucleotide
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Thioguanine / adverse effects*

Substances

  • Antimetabolites, Antineoplastic
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methyltransferases
  • thiopurine methyltransferase
  • Thioguanine