Jorgenson, H.G. and Elliott, M. and Allan, E.K. and Carr, C.E. and Holyoake, T.L. and Smith, K.D. (2002) Alpha1-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 0006-4971Full text not available in this repository. (Request a copy from the Strathclyde author)
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 alpha1-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.
|Keywords:||chronic myeloid leukemia , plasma, in vitro resistance, Pharmacy and materia medica, Biochemistry, Cell Biology, Immunology, Hematology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||12 Mar 2012 15:00|
|Last modified:||04 May 2016 12:57|