Drug transporters play a key role in the complex process of Imatinib resistance in vitro

Highlights • We establish the first Imatinib resistant cell line by discontinuous exposure. • This model elucidated the importance of treatment interruptions in resistance. • In both resistant models, efflux transporters were increased comparing to K562. • Influx transporters expression were diminis...

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Bibliographic Details
Published in:Leukemia research 2015-03, Vol.39 (3), p.355-360
Main Authors: Alves, Raquel, Fonseca, Ana Raquel, Gonçalves, Ana C, Ferreira-Teixeira, Margarida, Lima, Joana, Abrantes, Ana M, Alves, Vera, Rodrigues-Santos, Paulo, Jorge, Lénia, Matoso, Eunice, Carreira, Isabel M, Botelho, Maria Filomena, Sarmento-Ribeiro, Ana B
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Benzamides - pharmacology
Cell Proliferation - drug effects
CML
Drug Resistance, Neoplasm
Flow Cytometry
Fusion Proteins, bcr-abl - genetics
Hematology, Oncology and Palliative Medicine
Humans
Imatinib Mesylate
Imatinib resistance
In Situ Hybridization, Fluorescence
In Vitro Techniques
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism
Membrane drug transporters
OCT1
Organic Cation Transporter 1 - metabolism
P-glycoprotein
Piperazines - pharmacology
Protein Kinase Inhibitors - pharmacology
Pyrimidines - pharmacology
Therapeutic interruptions
Tumor Cells, Cultured
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Summary:Highlights • We establish the first Imatinib resistant cell line by discontinuous exposure. • This model elucidated the importance of treatment interruptions in resistance. • In both resistant models, efflux transporters were increased comparing to K562. • Influx transporters expression were diminished in both resistant cell lines. • Our results show the importance of ABC transporters as therapeutic targets.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2014.12.008