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

Blood
Niove E JordanidesJ C Mountford

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(+)) 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.

References

Jun 19, 2001·Biochimica Et Biophysica Acta·R W RobeyS E Bates
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Oct 24, 2002·Blood·Brian L AbbottBrian P Sorrentino
Mar 29, 2003·Journal of Hematotherapy & Stem Cell Research·Yalin GuoMonika Engelhardt
Nov 6, 2004·Blood·Lucy J ElrickTessa L Holyoake

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Citations

Apr 29, 2010·Current Hematologic Malignancy Reports·Mhairi Copland
Sep 24, 2010·Leukemia·I SlomaC J Eaves
Apr 4, 2008·Nature Reviews. Cancer·Michael Savona, Moshe Talpaz
Sep 15, 2007·Nature Reviews. Drug Discovery·Alfonso Quintás-CardamaJorge Cortes
Oct 9, 2013·The Journal of Experimental Medicine·Marina SchellerAchim Leutz
Apr 29, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Marius DohseSusan E Bates
Dec 16, 2010·The Journal of Clinical Investigation·Amie S CorbinBrian J Druker
Dec 17, 2008·Hematology·Junia V Melo, Charles Chuah
Feb 4, 2010·The Oncologist·Robert L Redner
Jan 1, 2009·OncoTargets and Therapy·Charles Chuah, Junia V Melo
Mar 9, 2010·Haematologica·Michael KoldehoffAhmet H Elmaagacli
Nov 14, 2013·International Journal of Pharmaceutics·Eva KraljAlbin Kristl
Jan 29, 2014·Medical Oncology·Luciene Terezina de LimaElvira M Guerra-Shinohara
Feb 9, 2011·Leukemia & Lymphoma·Joana M Diamond, Junia V Melo
Feb 9, 2011·Leukemia & Lymphoma·Birgitta Mitchell, Michael Deininger
Aug 28, 2009·Expert Opinion on Drug Metabolism & Toxicology·Yi An, Weg M Ongkeko
Jan 7, 2014·Expert Opinion on Biological Therapy·Alessandro MorottiGiuseppe Saglio
Jan 18, 2012·Biochemical Pharmacology·Karthika NatarajanDouglas D Ross
Nov 8, 2011·Hematology/oncology Clinics of North America·Jamshid S Khorashad, Michael W N Deininger
Nov 8, 2011·Hematology/oncology Clinics of North America·Paolo GallipoliTessa L Holyoake

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