The significance of enzyme and transporter polymorphisms for
imatinib plasma levels and achieving an optimal response in
chronic myeloid leukemia patients

J 2018

The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients

BELOHLAVKOVA, Petra, Filip VRBACKY, Jaroslava VOGLOVA, Zdeněk RÁČIL, Daniela ŽÁČKOVÁ et. al.

Basic information

Original name

The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients

Authors

BELOHLAVKOVA, Petra (203 Czech Republic, guarantor), Filip VRBACKY (203 Czech Republic), Jaroslava VOGLOVA (203 Czech Republic), Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), Katerina HROCHOVA (203 Czech Republic), Jana MALAKOVA (203 Czech Republic), Jiří MAYER (203 Czech Republic, belonging to the institution) and Pavel ZAK (203 Czech Republic)

Edition

Archives of Medical Science, Poland, Termedia Publishing House, 2018, 1734-1922

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Poland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.380

RIV identification code

RIV/00216224:14110/18:00105953

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.5114/aoms.2018.73538

UT WoS

000448045000023

Keywords in English

clinical response; imatinib; chronic myeloid leukemia; genetic polymorphisms

Abstract

V originále

Introduction: Imatinib mesylate is the drug of choice for patients with chronic myeloid leukemia (CML). Imatinib pharmacokinetics is affected by a number of transport proteins and enzymes. Material and methods: In the present study we evaluated the association of eight polymorphisms in the seven genes CYP3A5*3 (rs776746), CYP3A4*1 (rs2740574), CYP2C9*3 (rs1057910), SLC22A1 (rs683369), ABCB1 (rs1045642, rs1128503), ABCG2 (rs2231142) and ABCC2 (rs717620) with imatinib plasma level and achieving an optimal clinical response in 112 CML patients (53 men and 59 women). Results: No association was found between the examined polymorphisms in rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 and the achieved imatinib plasma level. The influence of rs776746 (CYP3A5*3) on the achievement of a complete cytogenetic response (CCyR) at 6 months was borderline non-significant (p = 0.06). Furthermore, no association was demonstrated between rs776746 polymorphisms and the achievement of a major molecular response (MMR) at 12 or 18 months. Polymorphisms rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 showed no impact on the optimal therapeutic response. Conclusions: Despite the results of some other studies, no other polymorphism we analyzed was associated with imatinib plasma level or clinical response. The treatment outcomes cannot be predicted using the candidate gene approach and treatment decisions cannot be made according to the polymorphisms investigated in this study.

Citovat

BELOHLAVKOVA, Petra, Filip VRBACKY, Jaroslava VOGLOVA, Zdeněk RÁČIL, Daniela ŽÁČKOVÁ, Katerina HROCHOVA, Jana MALAKOVA, Jiří MAYER and Pavel ZAK. The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients. Archives of Medical Science. Poland: Termedia Publishing House, 2018, vol. 14, No 6, p. 1416-1423. ISSN 1734-1922. Available from: https://dx.doi.org/10.5114/aoms.2018.73538.

@article{1491902,
   author = {Belohlavkova, Petra and Vrbacky, Filip and Voglova, Jaroslava and Ráčil, Zdeněk and Žáčková, Daniela and Hrochova, Katerina and Malakova, Jana and Mayer, Jiří and Zak, Pavel},
   article_location = {Poland},
   article_number = {6},
   doi = {http://dx.doi.org/10.5114/aoms.2018.73538},
   keywords = {clinical response; imatinib; chronic myeloid leukemia; genetic polymorphisms},
   language = {eng},
   issn = {1734-1922},
   journal = {Archives of Medical Science},
   title = {The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients},
   volume = {14},
   year = {2018}
}

TY  - JOUR
ID  - 1491902
AU  - Belohlavkova, Petra - Vrbacky, Filip - Voglova, Jaroslava - Ráčil, Zdeněk - Žáčková, Daniela - Hrochova, Katerina - Malakova, Jana - Mayer, Jiří - Zak, Pavel
PY  - 2018
TI  - The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients
JF  - Archives of Medical Science
VL  - 14
IS  - 6
SP  - 1416-1423
EP  - 1416-1423
PB  - Termedia Publishing House
SN  - 17341922
KW  - clinical response
KW  - imatinib
KW  - chronic myeloid leukemia
KW  - genetic polymorphisms
N2  - Introduction: Imatinib mesylate is the drug of choice for patients with chronic myeloid leukemia (CML). Imatinib pharmacokinetics is affected by a number of transport proteins and enzymes. Material and methods: In the present study we evaluated the association of eight polymorphisms in the seven genes CYP3A5*3 (rs776746), CYP3A4*1 (rs2740574), CYP2C9*3 (rs1057910), SLC22A1 (rs683369), ABCB1 (rs1045642, rs1128503), ABCG2 (rs2231142) and ABCC2 (rs717620) with imatinib plasma level and achieving an optimal clinical response in 112 CML patients (53 men and 59 women). Results: No association was found between the examined polymorphisms in rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 and the achieved imatinib plasma level. The influence of rs776746 (CYP3A5*3) on the achievement of a complete cytogenetic response (CCyR) at 6 months was borderline non-significant (p = 0.06). Furthermore, no association was demonstrated between rs776746 polymorphisms and the achievement of a major molecular response (MMR) at 12 or 18 months. Polymorphisms rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 showed no impact on the optimal therapeutic response. Conclusions: Despite the results of some other studies, no other polymorphism we analyzed was associated with imatinib plasma level or clinical response. The treatment outcomes cannot be predicted using the candidate gene approach and treatment decisions cannot be made according to the polymorphisms investigated in this study.
ER  -

BELOHLAVKOVA, Petra, Filip VRBACKY, Jaroslava VOGLOVA, Zdeněk RÁČIL, Daniela ŽÁČKOVÁ, Katerina HROCHOVA, Jana MALAKOVA, Jiří MAYER and Pavel ZAK. The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients. \textit{Archives of Medical Science}. Poland: Termedia Publishing House, 2018, vol.~14, No~6, p.~1416-1423. ISSN~1734-1922. Available from: https://dx.doi.org/10.5114/aoms.2018.73538.

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