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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1370-1373.
Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-02-003145.
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NEOPLASIA
Brief report
Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate
Niove E. Jordanides,
Heather G. Jorgensen,
Tessa L. Holyoake, and
Joanne C. Mountford
From the Experimental Haematology & Haemopoietic Stem Cells, Division of Cancer Sciences & Molecular Pathology, University of Glasgow; and the Scottish National Blood Transfusion Service, Glasgow Royal Infirmary, United Kingdom.
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+) cells. We have described a population of primitive Ph+ 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+ 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.
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