AI Article Synopsis

  • A new biochip method was created to identify BCR-ABL mutations linked to resistance against tyrosine kinase inhibitors, focusing on the tyrosine kinase domain.
  • The method combines RT-PCR with allele-specific hybridization on a biochip that tests for 11 key mutations, which are responsible for around 85% of imatinib resistance cases.
  • This technique was validated using clinical samples from chronic myeloid leukemia patients and proved highly sensitive in detecting the critical mutation T315I even in samples with low concentrations of leukemic cells.

Article 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.

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http://dx.doi.org/10.7868/S0026898416020087DOI Listing

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