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Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 5, pp 1155–1159 | Cite as

Thiopurine methyltransferase polymorphisms and mercaptopurine tolerance in Turkish children with acute lymphoblastic leukemia

  • Meryem Albayrak
  • Uljan Konyssova
  • Zuhre Kaya
  • Turkiz Gursel
  • Sezen Guntekin
  • E. Ferda Percin
  • Ulker Kocak
Original Article

Abstract

Purpose

Thiopurine methyltransferase (TPMT) enzyme is involved in the metabolism of 6-mercaptopurine (6-MP), a key component of acute lymphoblastic leukemia (ALL) treatment protocols in children. The aims of this study were to investigate the frequency of common genetic polymorphisms associated with low TPMT activity and correlations of polymorphic variants with 6-MP tolerance in a group of Turkish children with ALL.

Methods

Genotyping for G238C, A719G, and G460A mutations were performed by using NanoChip Technology. Adverse reactions during the first 6 months of maintenance therapy with oral 6-MP and methotrexate were retrospectively analyzed from patient’s files.

Results

Five (8.6%) of 58 children with ALL had a polymorphic TPMT allele: 4 (3.4%) were heterozygous for TPMT*3A (G460A and A719G), and one (0.9%) was heterozygous for TPMT*3C (A719G). No cases with TPMT*3B (G460A) or TPMT*2 (G238C) variants were identified. Children with TPMT*3A and *3C had significantly lower leukocyte and neutrophil counts and percentage of target 6-MP dosage, and longer periods with ≥grade 2 infections, ≥grade 2 liver toxicity, and chemotherapy interruptions than the children with wild-type TPMT during the first 24 weeks of maintenance therapy.

Conclusions

The frequency and distribution of common TPMT polymorphisms in Turkish children with ALL is similar to other Caucasian populations. Polymorphic variants were associated with excessive 6-MP toxicity supporting the suggestion that TPMT genotyping should be performed before institution of 6-MP therapy.

Keywords

Thiopurine methyltransferase polymorphisms Mercaptopurine Children Leukemia 

Notes

Acknowledgments

This study was supported in part by Grant No. 01/2008-38 from Gazi University.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Meryem Albayrak
    • 1
    • 3
  • Uljan Konyssova
    • 1
  • Zuhre Kaya
    • 1
  • Turkiz Gursel
    • 1
  • Sezen Guntekin
    • 2
  • E. Ferda Percin
    • 2
  • Ulker Kocak
    • 1
  1. 1.Pediatric Hematology Unit of the Department of PediatricsMedical School of Gazi UniversityAnkaraTurkey
  2. 2.Department of Clinical GeneticsMedical School of Gazi UniversityAnkaraTurkey
  3. 3.Çankaya, AnkaraTurkey

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