Chronic myeloid leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 activity.

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Engler JR, Frede A, Saunders VA, Zannettino AC, Hughes TP, White DL

Chronic myeloid leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 activity.

Leukemia. 2010 Apr;24(4):765-70. doi: 10.1038/leu.2010.16. Epub 2010 Feb 11.

PubMed ID

20147974 [ View in PubMed

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Abstract

Active influx of imatinib in chronic myeloid leukemia (CML) cells is mediated by the organic cation transporter 1 (OCT-1). Functional activity of OCT-1 (OCT-1 Activity) in mononuclear cells is an excellent predictor of molecular response over the first 24 months of imatinib therapy for chronic phase patients. CML progenitor cells are less sensitive to imatinib-induced apoptosis and are likely contributors to disease persistence. We investigated whether alterations in the expression and function of OCT-1 have a role in imatinib resistance in progenitors. We found the intracellular uptake and retention (IUR) of imatinib, OCT-1 Activity and OCT-1 mRNA expression are all significantly lower in CML CD34+ cells compared with mature CD34- cells (P<0.001). However, no differences in IUR or OCT-1 Activity were observed between these subsets in healthy donors. In contrast to OCT-1, ABCB1 and ABCG2 seemed to have no functional role in the transport of imatinib in CML CD34+ cells. Consistent with the observation that nilotinib uptake is not OCT-1 dependent, the IUR of nilotinib did not differ between CML CD34+ and CD34- cells. These results indicate that low imatinib accumulation in primitive CML cells, mediated through reduced OCT-1 Activity may be a critical determinant of long-term disease persistence.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Imatinib	Solute carrier family 22 member 1	Protein	Humans	No	Substrate	Details