[An alternative Abl-kinase inhibitor overcomes imatinib resistance mutations of Bcr-Abl oncogenes]

Posted by rob on October 28, 2004 under Uncategorized | Be the First to Comment

Dtsch Med Wochenschr. 2004 Oct 1; 129(40): 2100-3
Von Bubnoff N, Peschel C, Duyster J

BACKGROUND AND OBJECTIVE: The tyrosinkinase inhibitor Imatinib is active in Philadelphia-positive (Ph+) leukemia. Mutations within the Bcr-Abl kinase domain represent the major cause for clinical resistance toward imatinib. We aimed to examine, whether the alternative Abl Kinaseinhibitor SKI-DV 2 – 43 may be capable of suppressing the growth of cells expressing mutant forms of Bcr-Abl. METHODS: The proliferation of cells expressing wild-type and mutant forms of Bcr-Abl was measured in the presence of imatinib or the pyrido-pyrimidine SKI-DV 2 – 43. RESULTS: The growth of a cell line expressing wild-type Bcr-Abl was suppressed with higher potency in the presence of SKI-DV 2 – 43 when compared to imatinib. Moreover, SKI-DV 2 – 43 effectively suppressed mutant forms of Bcr-Abl that cause imatinib resistance in patients. CONCLUSION: Therefore, alternative Abl kinase inhibitors might play an important role in the future therapy of Philadelphia-positive leukemias.

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