Rapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays

Cameron C. Yin, Jorge Cortes, John Galbincea, Neelima Reddy, Megan Breeden, Elias Jabbour, Rajyalakshmi Luthra, Dan Jones

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)2005-2010
Number of pages6
JournalCancer Science
Volume101
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphotransferases
Mutation
Protein-Tyrosine Kinases
Therapeutics
Polymerase Chain Reaction
Point Mutation
Clone Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays. / Yin, Cameron C.; Cortes, Jorge; Galbincea, John; Reddy, Neelima; Breeden, Megan; Jabbour, Elias; Luthra, Rajyalakshmi; Jones, Dan.

In: Cancer Science, Vol. 101, No. 9, 01.09.2010, p. 2005-2010.

Research output: Contribution to journalArticle

Yin, Cameron C. ; Cortes, Jorge ; Galbincea, John ; Reddy, Neelima ; Breeden, Megan ; Jabbour, Elias ; Luthra, Rajyalakshmi ; Jones, Dan. / Rapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays. In: Cancer Science. 2010 ; Vol. 101, No. 9. pp. 2005-2010.
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