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Alpha-1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571.

Jørgensen, Heather G, Elliott, Moira A, Allan, Elaine K, Carr, Christine E, Holyoake, Tessa L and Smith, Kevin (2002) Alpha-1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI571. Blood, 99 (2). pp. 713-715. ISSN 0006-4971,

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Abstract/Description

Despite the efficacy of STI571 (Glivec, Novartis, Basle, Switzerland) in treating chronic myeloid leukemia (CML), drug resistance has already been noted both in vitro and in vivo. As plasma proteins, including alpha-1-acid glycoprotein (AGP), may reduce drug efficacy through binding, AGP was investigated for its ability to interact with STI571.


At all stages of CML, AGP plasma level was significantly higher than in normal controls (P < .05). The glycoprotein was purified from normal plasma and individual chronic myeloid leukemia (CML) patients' plasma by low-pressure chromatography. The influence of 1-acid glycoprotein (AGP), in the presence of STI571, on the proliferation of Philadelphia chromosome-positive (Ph+) cells was examined. Normal AGP, even at supraphysiological concentrations, did not block the effect of STI571 on K562-cell proliferation in vitro. Moreover, CML-derived AGP failed to block the effect of STI571 on Ph+ cells in vitro. Thus, these in vitro findings suggest that AGP will not abrogate the antileukemic activity of STI571.

Item Type: Article
Print ISSN: 0006-4971,
Electronic ISSN: 1528-0020
Uncontrolled Keywords: STI57; chronic myeloid leukemia; alpha-1-acid glycoprotein; 1-acid glycoprotein; Philadelphia chromosome-positive (Ph+);
University Divisions/Research Centres: Faculty of Health, Life & Social Sciences > School of Life Sciences
Dewey Decimal Subjects: 600 Technology > 610 Medicine & health > 615 Pharmacology & therapeutics
500 Science > 570 Life sciences; biology > 572 Biochemistry
600 Technology > 610 Medicine & health > 612 Human physiology
Library of Congress Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Item ID: 1672
Depositing User: RAE Import
Date Deposited: 30 Jun 2008 11:49
Last Modified: 16 Aug 2013 15:10
URI: http://researchrepository.napier.ac.uk/id/eprint/1672

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