Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate

Holyoake, T.L., Jordanides, N., Jorgensen, H.G. and Mountford, J.C. (2006) Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood, 108(4), pp. 1370-1373. (doi:10.1182/blood-2006-02-003145)

Holyoake, T.L., Jordanides, N., Jorgensen, H.G. and Mountford, J.C. (2006) Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood, 108(4), pp. 1370-1373. (doi:10.1182/blood-2006-02-003145)

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Abstract

Imatinib mesylate (IM) therapy for chronic myeloid leukemia (CML) has transformed the treatment of this disease. However, the vast majority of patients, despite major responses, still harbor Philadelphia chromosome-positive (Ph<sup>+</sup>) cells. We have described a population of primitive Ph<sup>+</sup> cells that are insensitive to IM and may be a source of IM resistance. Cell line studies have suggested that the drug transporter ABCG2 may be a mediator of IM resistance, however there is considerable debate about whether IM is an ABCG2 substrate or inhibitor. We demonstrate here that primitive CML CD34<sup>+</sup> cells aberrantly overexpress functional ABCG2 but that cotreatment with IM and an ABCG2 inhibitor does not potentiate the effect of IM. We definitively show that IM is an inhibitor of, but not a substrate for, ABCG2 and that, therefore, ABCG2 does not modulate intracellular concentrations of IM in this clinically relevant cell population.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jordanides, Ms Niove and Holyoake, Professor Tessa and Mountford, Dr Joanne and Jorgensen, Dr Heather
Authors: Holyoake, T.L., Jordanides, N., Jorgensen, H.G., and Mountford, J.C.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Blood
ISSN:0006-4971

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