Abstract
Tyrosine kinase inhibitors (TKIs) are the effective treatments for chronic myeloid leukemia (CML). However, clinical resistance to TKIs that leads to patient relapse remains a challenge. Acquisition of BCR-ABL mutations is crucial in the resistance but the underlying molecular mechanisms are poorly understood. Here we describe a cell culture model for CML acquired resistance in which blast crisis CML cells undergo initial apoptosis upon treatment with therapeutically effective doses of TKIs, but the cells regrow quickly with development of resistance through BCR-ABL mutations. This model mimics the clinical process of acquisition of BCR-ABL mutations and will be an important tool to dissect molecular mechanisms of CML drug resistance and to explore strategies to overcome resistance.
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Acknowledgement
This study was supported by grants from the US Department of Defense W81XWH-06-1-0268, the STOPCANCER Foundation, the V-Foundation, and the National Cancer Institute R01 CA143421. The core facilities including Analytical Cytometry Core and DNA Sequencing Core were supported by NCI P30 CA033572. The contents are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute or NIH.
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Wang, Z., Chen, W. (2016). A Convenient Cell Culture Model for CML Acquired Resistance Through BCR-ABL Mutations. In: Li, S., Zhang, H. (eds) Chronic Myeloid Leukemia. Methods in Molecular Biology, vol 1465. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-4011-0_13
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DOI: https://doi.org/10.1007/978-1-4939-4011-0_13
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