Determination of alpha-1 acid glycoprotein in patients with Ph+ chronic myeloid leukemia during the first 13 weeks of therapy with STI571.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 9509932 Publication Model: Print Cited Medium: Print ISSN: 1079-9796 (Print) Linking ISSN: 10799796 NLM ISO Abbreviation: Blood Cells Mol Dis Subsets: MEDLINE
    • Publication Information:
      Publication: <1996-> : Orlando, FL : Academic Press
      Original Publication: La Jolla, Calif. : Blood Cells Foundation, 1995-
    • Subject Terms:
      Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy ; Orosomucoid/*metabolism ; Piperazines/*pharmacology ; Pyrimidines/*pharmacology; Aged ; Benzamides ; Biomarkers, Tumor/blood ; Case-Control Studies ; Disease Progression ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Male ; Middle Aged ; Orosomucoid/genetics ; Piperazines/administration & dosage ; Prognosis ; Pyrimidines/administration & dosage ; RNA, Messenger/blood ; Time Factors ; Tumor Cells, Cultured
    • Abstract:
      The tyrosine kinase activity of the BCR/ABL fusion protein is required for the transformation in patients with chronic myeloid leukemia. The tyrosine kinase inhibitor STI571 inhibits the BCR/ABL and ABL kinase activity and consequently inhibits growth of BCR/ABL-positive cells. However, resistance to STI571 has been demonstrated in Ph+ cell lines and in CML patients and can be explained in some cases by point mutations within the ATP-binding pocket or amplification of the bcr/abl gene. In previous investigations using a nu/nu mouse model, the binding of STI571 to elevated levels of the plasmaprotein -1 acid glycoprotein (AGP) was identified as an additional mechanism of resistance to this therapeutic approach. Here we provide data on the expression of AGP in CML patients under therapy with STI571. Patients received 400 or 600 mg STI571 daily and apart from clinical parameters we determined AGP and C-reactive protein (CRP) plasma levels as well as the quantitative expression of both BCR/ABL and AGP mRNA in peripheral blood cells. Our data suggest that despite elevated AGP levels in 52% of our patients, no upfront resistance against STI571 was present. In conclusion, we demonstrated that during the first 13 weeks of STI571 therapy (i) plasma AGP levels in CML patients correlate with white blood cell count and stage of disease; (ii) patients with elevated AGP responded less rapidly to STI571; (iii) elevated AGP and CRP levels normalized in patients during treatment with STI571, although mRNA levels of AGP remained stable; (iv) initially normal levels of AGP remained in the normal range during treatment with STI571, indicating that STI571 does not trigger AGP expression in humans; and (v) in relapsed patients, elevation of AGP levels is present prior to hematological progress.
    • Accession Number:
      0 (Benzamides)
      0 (Biomarkers, Tumor)
      0 (Orosomucoid)
      0 (Piperazines)
      0 (Pyrimidines)
      0 (RNA, Messenger)
      8A1O1M485B (Imatinib Mesylate)
    • Publication Date:
      Date Created: 20020504 Date Completed: 20030618 Latest Revision: 20191105
    • Publication Date:
      20231215
    • Accession Number:
      10.1006/bcmd.2002.0493
    • Accession Number:
      11987244