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.

Základní údaje

Originální název

Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation

Autoři

Vydání

Oncology, Basel, Karger, 2014, 0030-2414

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 2.422

Kód RIV

RIV/00216224:14110/14:00076840

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1159/000357407

UT WoS

000335939300004

EID Scopus

2-s2.0-84895931601

Klíčová slova anglicky

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

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 2. 2015 22:07, Ing. Mgr. Věra Pospíšilíková

Anotace

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

Návaznosti

LM2011017, projekt VaV

Název: Advanced Cell Immunotherapy Unit - ACIU

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Advanced cell immunotherapy unit BVI-ACIU

MUNI/A/0964/2012, interní kód MU

Název: Inovativní léčebné postupy a toxicita léčby v dětské onkologii (Akronym: Invatidon II)

Investor: Masarykova univerzita, Inovativní léčebné postupy a toxicita léčby v dětské onkologii, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

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 a Dalibor VALÍK. Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation. Oncology. Basel: Karger, 2014, roč. 86, č. 3, s. 152-158. ISSN 0030-2414. Dostupné z: https://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 = {https://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 a Dalibor VALÍK. Augmenting Clinical Interpretability of Thiopurine Methyltransferase Laboratory Evaluation. \textit{Oncology}. Basel: Karger, 2014, roč.~86, č.~3, s.~152-158. ISSN~0030-2414. Dostupné z: https://doi.org/10.1159/000357407.

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