Real-time quantitative PCR analysis can be used as a primary screen

Posted by rob on July 27, 2004 under Uncategorized | Be the First to Comment

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

Autor(en): Branford S, Rudzki Z, Parkinson I, Grigg A, Taylor K, Seymour JF, Durrant S, Browett P, Schwarer AP, Arthur C, Catalano J, Leahy M, Filshie R, Bradstock K, Herrmann R, Joske D, Lynch K, Hughes T
Quelle: Blood 2004 Jul 15;.

Abstract: Mutations within the BCR-ABL kinase domain in imatinib-treated chronic myeloid leukemia are the main mechanism of acquired resistance. The early detection of mutations should provide clinical benefit by allowing early intervention. Quantitative PCR results of BCR-ABL mRNA were correlated with mutation analysis in 214 imatinib-treated patients. We determined whether there was a difference in the incidence of mutations between the patients with a greater than 2-fold rise in BCR-ABL and those with stable or decreasing levels. Of the 56 patients with a greater than 2-fold rise, 34 (61%) had detectable mutations (median rise 3.0-fold, 25th to 75th percentiles, 2.3 to 5.2). In 31 of these 34 patients (91%), the mutation was present at the time of the rise and became detectable within 3 months in the remaining patients. Only 1 of 158 patients (0.6%) with stable or decreasing BCR-ABL levels had a detectable mutation, P<0.0001. Thus a greater than 2-fold rise identified 34 of 35 patients (97%) 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.

http://www.bloodjournal.org/cgi/reprint/2004-03-1134v1.pdf?ck=nck