Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336
- 1 August 2002
- journal article
- Published by American Society of Hematology in Blood
- Vol. 100 (3) , 1068-1071
- https://doi.org/10.1182/blood.v100.3.1068
Abstract
The development of chronic myeloid leukemia (CML) is dependent on the deregulated tyrosine kinase of the oncoprotein BCR-ABL. STI571 (imatinib mesylate), an abl tyrosine kinase inhibitor, has proven remarkably effective for the treatment of CML. However, resistance to STI571 because of enhanced expression or mutation of theBCR-ABL gene has been detected in patients. In the current study we show that the farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits the proliferation of STI571-resistant BCR-ABL–positive cell lines and hematopoietic colony formation from peripheral blood samples of STI571-resistant patients with CML. Moreover, SCH66336 enhances STI571-induced apoptosis in STI571-sensitive cells and, in patients with STI571 resistance from gene amplification, cooperates with STI571 to induce apoptosis. Our data provide a rationale for combination clinical trials of STI571 and SCH66336 in CML patients and suggest that combination therapy may be effective in patients with STI571 resistance.Keywords
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