Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to sTI571

H.G. Jorgenson, M. Elliott, E.K. Allan, C.E. Carr, T.L. Holyoake, K.D. Smith

Research output: Contribution to journalArticle

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Abstract

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.
LanguageEnglish
Pages713-715
Number of pages3
JournalBlood
Volume99
Issue number2
DOIs
Publication statusPublished - 2002

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Glycoproteins
Plasmas
Acids
Orosomucoid
Philadelphia Chromosome
K562 Cells
Cell proliferation
Chromosomes
Chromatography
Imatinib Mesylate
In Vitro Techniques
Switzerland
Drug Resistance
Pharmaceutical Preparations
Blood Proteins
Cell Proliferation
Pressure

Keywords

  • chronic myeloid leukemia
  • plasma
  • in vitro resistance

Cite this

Jorgenson, H.G. ; Elliott, M. ; Allan, E.K. ; Carr, C.E. ; Holyoake, T.L. ; Smith, K.D. / Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to sTI571. In: Blood. 2002 ; Vol. 99, No. 2. pp. 713-715.
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Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to sTI571. / Jorgenson, H.G.; Elliott, M.; Allan, E.K.; Carr, C.E.; Holyoake, T.L.; Smith, K.D.

In: Blood, Vol. 99, No. 2, 2002, p. 713-715.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to sTI571

AU - Jorgenson, H.G.

AU - Elliott, M.

AU - Allan, E.K.

AU - Carr, C.E.

AU - Holyoake, T.L.

AU - Smith, K.D.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

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KW - in vitro resistance

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