Abstract
To identify a fast and sensitive method for screening for mutations in patients with imatinib- resistant chronic myeloid leukemia (CML), we compared allele specific oligonucleotide- polymerase chain reaction (ASO-PCR) assay with conventional direct sequencing. Among the 68 imatinib resistant CML patients studied, 18 amino acid substitutions were detected in 44 patients by two assays. The sensitivity of ASO-PCR was superior to that of direct sequencing as it could detect one mutant allele in 100 approximately 100,000 wild type sequences. The fastness, simplicity, and sensitivity of ASO-PCR assays will be useful for routine monitoring of mutations, especially for frequently identified mutations.
Publication types
-
Comparative Study
-
Evaluation Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alleles
-
Amino Acid Substitution
-
Antineoplastic Agents / pharmacology*
-
Antineoplastic Agents / therapeutic use
-
Benzamides
-
Drug Resistance, Neoplasm / genetics*
-
Fusion Proteins, bcr-abl / antagonists & inhibitors
-
Fusion Proteins, bcr-abl / genetics*
-
Genes, abl*
-
Genetic Testing / methods*
-
Humans
-
Imatinib Mesylate
-
K562 Cells / drug effects
-
K562 Cells / enzymology
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
-
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
-
Mutation, Missense
-
Piperazines / pharmacology*
-
Piperazines / therapeutic use
-
Point Mutation
-
Polymerase Chain Reaction / methods*
-
Protein Kinase Inhibitors / pharmacology*
-
Protein Kinase Inhibitors / therapeutic use
-
Pyrimidines / pharmacology*
-
Pyrimidines / therapeutic use
-
Sensitivity and Specificity
-
Sequence Analysis, DNA*
-
Time Factors
Substances
-
Antineoplastic Agents
-
Benzamides
-
Piperazines
-
Protein Kinase Inhibitors
-
Pyrimidines
-
Imatinib Mesylate
-
Fusion Proteins, bcr-abl