title: [Detection of BCR-ABL gene mutations in chronic myeloid leukemia using biochips].
abstract: A biochip-based method was developed to identify the BCR-ABL mutations that affect the thyrosine kinase domain and determine resistance to targeted therapy with thyrosine kinase inhibitors. The method is based on RT-PCR followed by allele-specific hybridization on a biochip with immobilized oligonucleotide probes. The biochip addresses 11 mutations, which are responsible for up to 85% of imatinib resistance cases. A method to decect the clinically significant mutation T315I was designed on the basis of LNA-clamped PCR and proved highly sensitive, detecting the mutation in clinical samples with a leukemic cell content of 5% or higher. The method was validated using clinical samples from chronic myeloid leukemia (CML) patients with acquired resistance to imatinib. The results of hybridization on biochip were verified by Sanger sequencing.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: A Yu
authors.initials: AY
authors.lastname: Ikonnikova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: Yu E
authors.initials: YE
authors.lastname: Yatsenko
authors.affiliation: Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: O S
authors.initials: OS
authors.lastname: Kremenetskaya
authors.affiliation: Rogachev Federal Research Clinical Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation, Moscow, 117997, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Vinogradova
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: D O
authors.initials: DO
authors.lastname: Fesenko
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
authors.forename: I S
authors.initials: IS
authors.lastname: Abramov
authors.affiliation: Kirov Research Institute of Hematology and Blood Transfusion, Kirov, 610027, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Ovsepyan
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.|nased@eimb.ru.
authors.forename: T V
authors.initials: TV
authors.lastname: Nasedkina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D000069439:Dasatinib / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib
keywords: chimeric gene BCR-ABL; chronic myeloid leukemia; imatinib resistance; mutations