Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations

Susan Branford, Zbigniew Rudzki, Ian Parkinson, Andrew Grigg, Kerry Taylor, John F. Seymour, Simon Durrant, Peter Browett, Anthony P. Schwarer, Chris Arthur, John Catalano, Michael F. Leahy, Robin Filshie, Kenneth Bradstock, Richard Herrmann, David Joske, Kevin Lynch, Tim Hughes

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

Mutations within the BCR-ABL kinase domain in imafinib-treated chronic myeloid leukemia (CML) are the main mechanism of acquired resistance. The early detection of mutations should provide clinical benefit by allowing early intervention. Quantitative polymerase chain reaction (RQ-PCR) results of BCR-ABL mRNA were correlated with mutation analysis in 214 patients treated with imatinib. We determined whether there was a difference in the incidence of mutations between the patients with a more than 2-fold rise in BCR-ABL and patients with stable or decreasing levels. Of the 56 patients with a more than 2-fold rise, 34 (61%) had detectable mutations (median rise, 3.0-fold; 25th-75th percentiles, 2.3-5.2). In 31 (91%) of these 34 patients, the mutation was present at the time of the rise and became detectable within 3 months in the remaining patients. Only 1 (0.6%) of 158 patients with stable or decreasing BCR-ABL levels had a detectable mutation, P less than .0001. Thus, a more than 2-fold rise identified 34 (97%) of 35 patients with a mutation. We conclude that a rise in BCR-ABL of more than 2-fold can be used as a primary indicator to test patients for BCR-ABL kinase domain mutations.

LanguageEnglish
Pages2926-2932
Number of pages7
JournalBlood
Volume104
Issue number9
DOIs
Publication statusPublished - 1 Nov 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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