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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2011

01-11-2011 | Original Article

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

Authors: Meryem Albayrak, Uljan Konyssova, Zuhre Kaya, Turkiz Gursel, Sezen Guntekin, E. Ferda Percin, Ulker Kocak

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2011

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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.
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Metadata
Title
Thiopurine methyltransferase polymorphisms and mercaptopurine tolerance in Turkish children with acute lymphoblastic leukemia
Authors
Meryem Albayrak
Uljan Konyssova
Zuhre Kaya
Turkiz Gursel
Sezen Guntekin
E. Ferda Percin
Ulker Kocak
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1599-7

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