Augmenting Clinical Interpretability of Thiopurine
Methyltransferase Laboratory Evaluation

J 2014

Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation

DEMLOVÁ, Regina, Martina MRKVICOVA, Jaroslav ŠTĚRBA, Hana BERNATÍKOVÁ, Jan STARY et. al.

Basic information

Original name

Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation

Authors

DEMLOVÁ, Regina (203 Czech Republic, guarantor, belonging to the institution), Martina MRKVICOVA (203 Czech Republic), Jaroslav ŠTĚRBA (203 Czech Republic), Hana BERNATÍKOVÁ (203 Czech Republic), Jan STARY (203 Czech Republic), Martina SUKOVA (203 Czech Republic), Alena MIKUŠKOVÁ (203 Czech Republic, belonging to the institution), Alica CHOCHOLOVA (703 Slovakia), Beata MLADOSIEVICOVA (703 Slovakia), Andrea SOLTYSOVA (203 Czech Republic), Darina BEHULOVA (703 Slovakia), Kateřina PILÁTOVÁ (203 Czech Republic), Lenka ZDRAŽILOVÁ DUBSKÁ (203 Czech Republic, belonging to the institution) and Dalibor VALÍK (203 Czech Republic)

Edition

Oncology, Basel, Karger, 2014, 0030-2414

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.422

RIV identification code

RIV/00216224:14110/14:00076840

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1159/000357407

UT WoS

000335939300004

Keywords in English

Acute lymphoblastic leukemia; Compound heterozygote; Genotype-phenotype correlation; Rate-blanked pharmacophenotyping; Thiopurine methyltransferase

Abstract

V originále

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

Links

LM2011017, research and development project

Name: Advanced Cell Immunotherapy Unit - ACIU

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/0964/2012, interní kód MU

Name: Inovativní léčebné postupy a toxicita léčby v dětské onkologii (Acronym: Invatidon II)

Investor: Masaryk University, Category A

Citovat

DEMLOVÁ, Regina, Martina MRKVICOVA, Jaroslav ŠTĚRBA, Hana BERNATÍKOVÁ, Jan STARY, Martina SUKOVA, Alena MIKUŠKOVÁ, Alica CHOCHOLOVA, Beata MLADOSIEVICOVA, Andrea SOLTYSOVA, Darina BEHULOVA, Kateřina PILÁTOVÁ, Lenka ZDRAŽILOVÁ DUBSKÁ and Dalibor VALÍK. Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation. Oncology. Basel: Karger, 2014, vol. 86, No 3, p. 152-158. ISSN 0030-2414. Available from: https://dx.doi.org/10.1159/000357407.

@article{1202692,
   author = {Demlová, Regina and Mrkvicova, Martina and Štěrba, Jaroslav and Bernatíková, Hana and Stary, Jan and Sukova, Martina and Mikušková, Alena and Chocholova, Alica and Mladosievicova, Beata and Soltysova, Andrea and Behulova, Darina and Pilátová, Kateřina and Zdražilová Dubská, Lenka and Valík, Dalibor},
   article_location = {Basel},
   article_number = {3},
   doi = {http://dx.doi.org/10.1159/000357407},
   keywords = {Acute lymphoblastic leukemia; Compound heterozygote; Genotype-phenotype correlation; Rate-blanked pharmacophenotyping; Thiopurine methyltransferase},
   language = {eng},
   issn = {0030-2414},
   journal = {Oncology},
   title = {Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation},
   volume = {86},
   year = {2014}
}

TY  - JOUR
ID  - 1202692
AU  - 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
PY  - 2014
TI  - Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation
JF  - Oncology
VL  - 86
IS  - 3
SP  - 152-158
EP  - 152-158
PB  - Karger
SN  - 00302414
KW  - Acute lymphoblastic leukemia
KW  - Compound heterozygote
KW  - Genotype-phenotype correlation
KW  - Rate-blanked pharmacophenotyping
KW  - Thiopurine methyltransferase
N2  - 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
ER  -

DEMLOVÁ, Regina, Martina MRKVICOVA, Jaroslav ŠTĚRBA, Hana BERNATÍKOVÁ, Jan STARY, Martina SUKOVA, Alena MIKUŠKOVÁ, Alica CHOCHOLOVA, Beata MLADOSIEVICOVA, Andrea SOLTYSOVA, Darina BEHULOVA, Kateřina PILÁTOVÁ, Lenka ZDRAŽILOVÁ DUBSKÁ and Dalibor VALÍK. Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation. \textit{Oncology}. Basel: Karger, 2014, vol.~86, No~3, p.~152-158. ISSN~0030-2414. Available from: https://dx.doi.org/10.1159/000357407.

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