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https://hdl.handle.net/2440/60850
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dc.contributor.author | Engler, J. | - |
dc.contributor.author | Frede, A. | - |
dc.contributor.author | Saunders, V. | - |
dc.contributor.author | Zannettino, A. | - |
dc.contributor.author | Hughes, T. | - |
dc.contributor.author | White, D. | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Leukemia, 2010; 24(4):765-770 | - |
dc.identifier.issn | 0887-6924 | - |
dc.identifier.issn | 1476-5551 | - |
dc.identifier.uri | http://hdl.handle.net/2440/60850 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | J.R. Engler, A. Frede, V.A. Saunders, A.C.W. Zannettino, T.P. Hughes, and D.L. White | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | © 2010 Macmillan Publishers Limited. All rights reserved | - |
dc.source.uri | http://dx.doi.org/10.1038/leu.2010.16 | - |
dc.subject | CML | - |
dc.subject | OCT-1 | - |
dc.subject | OCT-1 Activity | - |
dc.subject | CD34+ | - |
dc.subject | imatinib | - |
dc.title | Chronic Myeloid Leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 Activity | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/leu.2010.16 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Zannettino, A. [0000-0002-6646-6167] | - |
dc.identifier.orcid | Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509] | - |
dc.identifier.orcid | White, D. [0000-0003-4844-333X] | - |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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