Imatinib Mesylate Resistance Through BCR-ABL Independence in Chronic Myelogenous Leukemia
Open Access
- 15 January 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 64 (2) , 672-677
- https://doi.org/10.1158/0008-5472.can-03-1484
Abstract
Imatinib mesylate (IM) binds to the BCR-ABL protein, inhibiting its kinase activity and effectively controlling diseases driven by this kinase. IM resistance has been associated with kinase mutations or increased BCR-ABL expression. However, disease progression may be mediated by other mechanisms that render tumor cells independent of BCR-ABL. To demonstrate this potential, IM-resistant cells were found in chronic myelogenous leukemia patients with continuous BCR-ABL gene expression but undetectable BCR-ABL protein expression. These cells were unresponsive to IM and acquired BCR-ABL-independent signaling characteristics. IM resistance in some patients may be mediated through loss of kinase target dependence.Keywords
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