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MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients

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MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients. / Harrach, S; Schmidt-Lauber, C; Pap, T; Pavenstädt, H; Schlatter, E; Schmidt, E; Berdel, W E; Schulze, U; Edemir, B; Jeromin, S; Haferlach, T; Ciarimboli, G; Bertrand, J.

In: BLOOD CANCER J, Vol. 6, No. 9, 16.09.2016, p. e470.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Harrach, S, Schmidt-Lauber, C, Pap, T, Pavenstädt, H, Schlatter, E, Schmidt, E, Berdel, WE, Schulze, U, Edemir, B, Jeromin, S, Haferlach, T, Ciarimboli, G & Bertrand, J 2016, 'MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients', BLOOD CANCER J, vol. 6, no. 9, pp. e470. https://doi.org/10.1038/bcj.2016.79

APA

Harrach, S., Schmidt-Lauber, C., Pap, T., Pavenstädt, H., Schlatter, E., Schmidt, E., Berdel, W. E., Schulze, U., Edemir, B., Jeromin, S., Haferlach, T., Ciarimboli, G., & Bertrand, J. (2016). MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients. BLOOD CANCER J, 6(9), e470. https://doi.org/10.1038/bcj.2016.79

Vancouver

Harrach S, Schmidt-Lauber C, Pap T, Pavenstädt H, Schlatter E, Schmidt E et al. MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients. BLOOD CANCER J. 2016 Sep 16;6(9):e470. https://doi.org/10.1038/bcj.2016.79

Bibtex

@article{61be1ce2556846c89e325e6353c2893e,
title = "MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients",
abstract = "Although imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), 25-30% patients do not respond or relapse after initial response. Imatinib uptake into targeted cells is crucial for its molecular response and clinical effectiveness. The organic cation transporter 1 (OCT1) has been proposed to be responsible for this process, but its relevance has been discussed controversially in recent times. Here we found that the multidrug and toxin extrusion protein 1 (MATE1) transports imatinib with a manifold higher affinity. MATE1 mainly mediates the cellular uptake of imatinib into targeted cells and thereby controls the intracellular effectiveness of imatinib. Importantly, MATE1 but not OCT1 expression is reduced in total bone marrow cells of imatinib-non-responding CML patients compared with imatinib-responding patients, indicating that MATE1 but not OCT1 determines the therapeutic success of imatinib. We thus propose that imatinib non-responders could be identified early before starting therapy by measuring MATE1 expression levels.",
keywords = "Adult, Aged, Antineoplastic Agents/pharmacology, Cell Line, Tumor, Drug Resistance, Neoplasm, Female, Fusion Proteins, bcr-abl/genetics, Gene Expression, Gene Knockdown Techniques, Humans, Imatinib Mesylate/pharmacology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics, Male, Middle Aged, Organic Cation Transport Proteins/genetics, Organic Cation Transporter 1/genetics, Protein Kinase Inhibitors/pharmacology, RNA Interference",
author = "S Harrach and C Schmidt-Lauber and T Pap and H Pavenst{\"a}dt and E Schlatter and E Schmidt and Berdel, {W E} and U Schulze and B Edemir and S Jeromin and T Haferlach and G Ciarimboli and J Bertrand",
year = "2016",
month = sep,
day = "16",
doi = "10.1038/bcj.2016.79",
language = "English",
volume = "6",
pages = "e470",
journal = "BLOOD CANCER J",
issn = "2044-5385",
publisher = "NATURE PUBLISHING GROUP",
number = "9",

}

RIS

TY - JOUR

T1 - MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients

AU - Harrach, S

AU - Schmidt-Lauber, C

AU - Pap, T

AU - Pavenstädt, H

AU - Schlatter, E

AU - Schmidt, E

AU - Berdel, W E

AU - Schulze, U

AU - Edemir, B

AU - Jeromin, S

AU - Haferlach, T

AU - Ciarimboli, G

AU - Bertrand, J

PY - 2016/9/16

Y1 - 2016/9/16

N2 - Although imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), 25-30% patients do not respond or relapse after initial response. Imatinib uptake into targeted cells is crucial for its molecular response and clinical effectiveness. The organic cation transporter 1 (OCT1) has been proposed to be responsible for this process, but its relevance has been discussed controversially in recent times. Here we found that the multidrug and toxin extrusion protein 1 (MATE1) transports imatinib with a manifold higher affinity. MATE1 mainly mediates the cellular uptake of imatinib into targeted cells and thereby controls the intracellular effectiveness of imatinib. Importantly, MATE1 but not OCT1 expression is reduced in total bone marrow cells of imatinib-non-responding CML patients compared with imatinib-responding patients, indicating that MATE1 but not OCT1 determines the therapeutic success of imatinib. We thus propose that imatinib non-responders could be identified early before starting therapy by measuring MATE1 expression levels.

AB - Although imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), 25-30% patients do not respond or relapse after initial response. Imatinib uptake into targeted cells is crucial for its molecular response and clinical effectiveness. The organic cation transporter 1 (OCT1) has been proposed to be responsible for this process, but its relevance has been discussed controversially in recent times. Here we found that the multidrug and toxin extrusion protein 1 (MATE1) transports imatinib with a manifold higher affinity. MATE1 mainly mediates the cellular uptake of imatinib into targeted cells and thereby controls the intracellular effectiveness of imatinib. Importantly, MATE1 but not OCT1 expression is reduced in total bone marrow cells of imatinib-non-responding CML patients compared with imatinib-responding patients, indicating that MATE1 but not OCT1 determines the therapeutic success of imatinib. We thus propose that imatinib non-responders could be identified early before starting therapy by measuring MATE1 expression levels.

KW - Adult

KW - Aged

KW - Antineoplastic Agents/pharmacology

KW - Cell Line, Tumor

KW - Drug Resistance, Neoplasm

KW - Female

KW - Fusion Proteins, bcr-abl/genetics

KW - Gene Expression

KW - Gene Knockdown Techniques

KW - Humans

KW - Imatinib Mesylate/pharmacology

KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics

KW - Male

KW - Middle Aged

KW - Organic Cation Transport Proteins/genetics

KW - Organic Cation Transporter 1/genetics

KW - Protein Kinase Inhibitors/pharmacology

KW - RNA Interference

U2 - 10.1038/bcj.2016.79

DO - 10.1038/bcj.2016.79

M3 - SCORING: Journal article

C2 - 27635733

VL - 6

SP - e470

JO - BLOOD CANCER J

JF - BLOOD CANCER J

SN - 2044-5385

IS - 9

ER -