Dissemin is shutting down on January 1st, 2025

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Springer Nature [academic journals on nature.com], British Journal of Cancer, 6(109), p. 1593-1598, 2013

DOI: 10.1038/bjc.2013.318

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BCR-ABL1 kinase domain mutations may persist at very low levels for many years and lead to subsequent TKI resistance

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

BACKGROUND: BCR-ABL1 mutation analysis is recommended for chronic myeloid leukaemia patients. However, mutations may become undetectable after changing therapy, and it is unknown whether they have been eradicated. METHODS: We examined longitudinal data of patients with imatinib-resistant mutations, which became undetectable by Sanger sequencing to determine whether mutations could reappear, and the related circumstances. RESULTS: Identical imatinib- and nilotinib-resistant mutations reappeared following further therapy changes in five patients, and was associated with subsequent nilotinib resistance in four. CONCLUSION: The data suggest that some BCR-ABL1 mutations may persist at undetectable levels for many years after changing therapy, and can be reselected and confer resistance to subsequent inhibitors. ; W T Parker, A L Yeoman, B A Jamison, D T Yeung, H S Scott, T P Hughes, and S Branford