Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells

Jueqiong Wang; Liu Lu; Chung H. Kok; Verity A. Saunders; Jarrad M. Goyne; Phuong Dang; Tamara M. Leclercq; Timothy P. Hughes; Deborah L. White

doi:10.3324/haematol.2016.153270

Haematologica (May 2017)

Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells

Jueqiong Wang,
Liu Lu,
Chung H. Kok,
Verity A. Saunders,
Jarrad M. Goyne,
Phuong Dang,
Tamara M. Leclercq,
Timothy P. Hughes,
Deborah L. White

Affiliations

Jueqiong Wang: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia;School of Medicine, University of Adelaide, Australia
Liu Lu: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia;School of Medicine, University of Adelaide, Australia
Chung H. Kok: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia;School of Medicine, University of Adelaide, Australia
Verity A. Saunders: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
Jarrad M. Goyne: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
Phuong Dang: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia
Tamara M. Leclercq: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia;School of Medicine, University of Adelaide, Australia
Timothy P. Hughes: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia;School of Medicine, University of Adelaide, Australia;Department of Haematology, SA Pathology, Adelaide, Australia;Australasian Leukaemia and Lymphoma Group, Melbourne, Australia
Deborah L. White: Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia;School of Medicine, University of Adelaide, Australia;Australasian Leukaemia and Lymphoma Group, Melbourne, Australia

DOI: https://doi.org/10.3324/haematol.2016.153270
Journal volume & issue: Vol. 102, no. 5

Abstract

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Imatinib is actively transported by organic cation transporter-1 (OCT-1) influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Herein we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor γ agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor γ antagonists (GW9662, T0070907) increase OCT-1 activity. Importantly, these effects can lead to corresponding changes in sensitivity to BCR-ABL kinase inhibition. Results were confirmed in peroxisome proliferator-activated receptor γ-transduced K562 cells. Furthermore, we identified a strong negative correlation between OCT-1 activity and peroxisome proliferator-activated receptor γ transcriptional activity in diagnostic chronic myeloid leukemia patients (n=84; P

Published in Haematologica

ISSN: 0390-6078 (Print); 1592-8721 (Online)
Publisher: Ferrata Storti Foundation
Country of publisher: Italy
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the blood and blood-forming organs
Website: http://www.haematologica.org

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