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https://hdl.handle.net/2440/5551
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Type: | Journal article |
Title: | 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 |
Author: | Branford, S. Rudzki, Z. Parkinson, I. Grigg, A. Taylor, K. Seymour, J. Durrant, S. Browett, P. Schwarer, A. Arthur, C. Catalano, J. Leahy, M. Filshie, R. Bradstock, K. Herrmann, R. Joske, D. Lynch, K. Hughes, T. |
Citation: | Blood, 2004; 104(9):2926-2932 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2004 |
ISSN: | 0006-4971 1528-0020 |
Abstract: | Mutations within the BCR-ABL kinase domain in imatinib-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. |
Keywords: | Humans Benzamides Piperazines Pyrimidines Fusion Proteins, bcr-abl RNA, Messenger Drug Monitoring Predictive Value of Tests Polymerase Chain Reaction DNA Mutational Analysis Protein Structure, Tertiary Drug Resistance, Neoplasm Leukemia, Myelogenous, Chronic, BCR-ABL Positive Imatinib Mesylate |
Description: | Copyright © 2004 by American Society of Hematology |
DOI: | 10.1182/blood-2004-03-1134 |
Published version: | http://dx.doi.org/10.1182/blood-2004-03-1134 |
Appears in Collections: | Aurora harvest Pathology publications |
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