The SNP rs460089 in the gene promoter of the drug transporter
OCTN1 has prognostic value for treatment-free remission in
chronic myeloid leukemia patients treated with imatinib

J 2024

The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib

POLAKOVA, Katerina Machova, Ali ALBEER, Vaclava POLIVKOVA, Monika KRUTSKA, Katerina VLCANOVA et. al.

Basic information

Original name

The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib

Authors

POLAKOVA, Katerina Machova, Ali ALBEER, Vaclava POLIVKOVA, Monika KRUTSKA, Katerina VLCANOVA, Nikola CURIK, Alice FABARIUS, Hana KLAMOVA, Birgit SPIESS, Cornelius F WALLER, Tim H BRUEMMENDORF, Jolanta DENGLER, Volker KUNZMANN, Andreas BURCHERT, Petra BELOHLAVKOVA, Satu MUSTJOKI, Edgar FABER, Jiří MAYER (203 Czech Republic, belonging to the institution), Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), Panayiotis PANAYIOTIDIS, Johan RICHTER, Henrik HJORTH-HANSEN, Magdalena KAMINSKA, Magdalena PLONKA, Elzbieta SZCZEPANEK, Monika SZAREJKO, Grazyna BOBER, Iwona HUS, Olga GRZYBOWSKA-IZYDORCZYK, Ewa WASILEWSKA, Edyta PACZKOWSKA, Joanna NIESIOBEDZKA-KREZEL, Krzysztof GIANNOPOULOS, Francois X MAHON, Tomasz SACHA, Susanne SAUSSELE and Markus PFIRRMANN

Edition

Leukemia, London, Nature Publishing Group, 2024, 0887-6924

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.400 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41375-023-02109-2

UT WoS

001129500800001

Keywords in English

chronic myeloid leukemia; imatinib

Abstract

V originále

Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.

Citovat

POLAKOVA, Katerina Machova, Ali ALBEER, Vaclava POLIVKOVA, Monika KRUTSKA, Katerina VLCANOVA, Nikola CURIK, Alice FABARIUS, Hana KLAMOVA, Birgit SPIESS, Cornelius F WALLER, Tim H BRUEMMENDORF, Jolanta DENGLER, Volker KUNZMANN, Andreas BURCHERT, Petra BELOHLAVKOVA, Satu MUSTJOKI, Edgar FABER, Jiří MAYER, Daniela ŽÁČKOVÁ, Panayiotis PANAYIOTIDIS, Johan RICHTER, Henrik HJORTH-HANSEN, Magdalena KAMINSKA, Magdalena PLONKA, Elzbieta SZCZEPANEK, Monika SZAREJKO, Grazyna BOBER, Iwona HUS, Olga GRZYBOWSKA-IZYDORCZYK, Ewa WASILEWSKA, Edyta PACZKOWSKA, Joanna NIESIOBEDZKA-KREZEL, Krzysztof GIANNOPOULOS, Francois X MAHON, Tomasz SACHA, Susanne SAUSSELE and Markus PFIRRMANN. The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib. Leukemia. London: Nature Publishing Group, 2024, vol. 38, No 2, p. 318-325. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/s41375-023-02109-2.

@article{2370258,
   author = {Polakova, Katerina Machova and Albeer, Ali and Polivkova, Vaclava and Krutska, Monika and Vlcanova, Katerina and Curik, Nikola and Fabarius, Alice and Klamova, Hana and Spiess, Birgit and Waller, Cornelius F and Bruemmendorf, Tim H and Dengler, Jolanta and Kunzmann, Volker and Burchert, Andreas and Belohlavkova, Petra and Mustjoki, Satu and Faber, Edgar and Mayer, Jiří and Žáčková, Daniela and Panayiotidis, Panayiotis and Richter, Johan and HjorthandHansen, Henrik and Kaminska, Magdalena and Plonka, Magdalena and Szczepanek, Elzbieta and Szarejko, Monika and Bober, Grazyna and Hus, Iwona and GrzybowskaandIzydorczyk, Olga and Wasilewska, Ewa and Paczkowska, Edyta and NiesiobedzkaandKrezel, Joanna and Giannopoulos, Krzysztof and Mahon, Francois X and Sacha, Tomasz and Saussele, Susanne and Pfirrmann, Markus},
   article_location = {London},
   article_number = {2},
   doi = {http://dx.doi.org/10.1038/s41375-023-02109-2},
   keywords = {chronic myeloid leukemia; imatinib},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib},
   url = {https://www.nature.com/articles/s41375-023-02109-2},
   volume = {38},
   year = {2024}
}

TY  - JOUR
ID  - 2370258
AU  - Polakova, Katerina Machova - Albeer, Ali - Polivkova, Vaclava - Krutska, Monika - Vlcanova, Katerina - Curik, Nikola - Fabarius, Alice - Klamova, Hana - Spiess, Birgit - Waller, Cornelius F - Bruemmendorf, Tim H - Dengler, Jolanta - Kunzmann, Volker - Burchert, Andreas - Belohlavkova, Petra - Mustjoki, Satu - Faber, Edgar - Mayer, Jiří - Žáčková, Daniela - Panayiotidis, Panayiotis - Richter, Johan - Hjorth-Hansen, Henrik - Kaminska, Magdalena - Plonka, Magdalena - Szczepanek, Elzbieta - Szarejko, Monika - Bober, Grazyna - Hus, Iwona - Grzybowska-Izydorczyk, Olga - Wasilewska, Ewa - Paczkowska, Edyta - Niesiobedzka-Krezel, Joanna - Giannopoulos, Krzysztof - Mahon, Francois X - Sacha, Tomasz - Saussele, Susanne - Pfirrmann, Markus
PY  - 2024
TI  - The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib
JF  - Leukemia
VL  - 38
IS  - 2
SP  - 318-325
EP  - 318-325
PB  - Nature Publishing Group
SN  - 08876924
KW  - chronic myeloid leukemia
KW  - imatinib
UR  - https://www.nature.com/articles/s41375-023-02109-2
N2  - Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
ER  -

POLAKOVA, Katerina Machova, Ali ALBEER, Vaclava POLIVKOVA, Monika KRUTSKA, Katerina VLCANOVA, Nikola CURIK, Alice FABARIUS, Hana KLAMOVA, Birgit SPIESS, Cornelius F WALLER, Tim H BRUEMMENDORF, Jolanta DENGLER, Volker KUNZMANN, Andreas BURCHERT, Petra BELOHLAVKOVA, Satu MUSTJOKI, Edgar FABER, Jiří MAYER, Daniela ŽÁČKOVÁ, Panayiotis PANAYIOTIDIS, Johan RICHTER, Henrik HJORTH-HANSEN, Magdalena KAMINSKA, Magdalena PLONKA, Elzbieta SZCZEPANEK, Monika SZAREJKO, Grazyna BOBER, Iwona HUS, Olga GRZYBOWSKA-IZYDORCZYK, Ewa WASILEWSKA, Edyta PACZKOWSKA, Joanna NIESIOBEDZKA-KREZEL, Krzysztof GIANNOPOULOS, Francois X MAHON, Tomasz SACHA, Susanne SAUSSELE and Markus PFIRRMANN. The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib. \textit{Leukemia}. London: Nature Publishing Group, 2024, vol.~38, No~2, p.~318-325. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/s41375-023-02109-2.

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