Abstract
Treatment of CML with the tyrosine kinase inhibitor (TKI) imatinib mesylate results in the emergence of point mutations within the kinase domain (KD) of the BCR-ABL1 fusion transcript. The introduction of next-generation TKIs that can overcome the effects of some BCR-ABL1 KD mutations requires quantitative mutation profiling methods to assess responses. We report the design and validation of such quantitative assays, using pyrosequencing and mutation-specific RT-PCR techniques, to allow sequential monitoring and illustrate their use in tracking specific KD mutations (e.g. G250E, T315I, and M351T) following changes in therapy. Pyrosequencing and mutation-specific RT-PCR allows sequential monitoring of specific mutations and identification of rapid clonal shifts in response to kinase inhibitor therapy in CML. Rapid reselection of TKI-resistant clones occurs following therapy switch in CML.
Original language | English (US) |
---|---|
Pages (from-to) | 2005-2010 |
Number of pages | 6 |
Journal | Cancer Science |
Volume | 101 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2010 |
Externally published | Yes |
ASJC Scopus subject areas
- Oncology
- Cancer Research