Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.

@article{Druker2001ActivityOA,
  title={Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome.},
  author={Brian J. Druker and Charles L. Sawyers and Hagop M. Kantarjian and Debra Resta and S F Reese and John M. Ford and Renaud Capdeville and Moshe Talpaz},
  journal={The New England journal of medicine},
  year={2001},
  volume={344 14},
  pages={
          1038-42
        }
}
BACKGROUND BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia chromosome. [] Key MethodMETHODS In this dose-escalating pilot study, 58 patients were treated with STI571; 38 patients had a myeloid blast crisis and 20 had ALL or a lymphoid blast crisis. Treatment was given orally at daily doses ranging from 300 to 1000 mg.

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STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
EFFICACY AND SAFETY OF A SPECIFIC INHIBITOR OF THE BCR-ABL TYROSINE KINASE IN CHRONIC MYELOID LEUKEMIA
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TLDR
Imatinib mesylate therapy was less toxic and produced a higher response rate, longer median survival, and lower 4-week induction mortality than standard cytarabine-based therapy, and is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.
Tyrosine kinase inhibitor as a therapeutic drug for chronic myelogenous leukemia and gastrointestinal stromal tumor.
  • M. Nakajima, W. Toga
  • Biology, Chemistry
    Nihon yakurigaku zasshi. Folia pharmacologica Japonica
  • 2003
TLDR
STI571 showed significant efficacy in the clinical study with CML patients at all stages: chronic phase, accelerated phase, and blast crisis, and certain point mutations in the ATP binding site were found to be a cause of resistance to STI571 in both Bcr-Abl and c-Kit kinases.
Determination of alpha-1 acid glycoprotein in patients with Ph+ chronic myeloid leukemia during the first 13 weeks of therapy with STI571.
TLDR
It is demonstrated that during the first 13 weeks of STI571 therapy, plasma AGP levels in CML patients correlate with white blood cell count and stage of disease; patients with elevated AGP responded less rapidly to STi571; and in relapsed patients, elevation ofAGP levels is present prior to hematological progress.
Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment.
TLDR
The data support that in CML patients treated with STI571, ABL mutations are not restricted to the accelerated phase of the disease and that, at least in some cases, mutations seem to occur prior to STi571 therapy, probably as second mutational events during the course of CML.
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