Publication details

Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation

Authors

DEMLOVÁ Regina MRKVICOVA Martina ŠTĚRBA Jaroslav BERNATÍKOVÁ Hana STARY Jan SUKOVA Martina MIKUŠKOVÁ Alena CHOCHOLOVA Alica MLADOSIEVICOVA Beata SOLTYSOVA Andrea BEHULOVA Darina PILÁTOVÁ Kateřina ZDRAŽILOVÁ DUBSKÁ Lenka VALÍK Dalibor

Year of publication 2014
Type Article in Periodical
Magazine / Source Oncology
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1159/000357407
Field Oncology and hematology
Keywords Acute lymphoblastic leukemia; Compound heterozygote; Genotype-phenotype correlation; Rate-blanked pharmacophenotyping; Thiopurine methyltransferase
Description Objective: Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported. Patients and Methods: The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method. Results: Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT*1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wildtype and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient. Conclusion: Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism. (C) 2014 S. Karger AG, Basel
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