HIGH-SENSITIVITY SEQUENCING TO DETECT BTK INHIBITOR RESISTANCE

摘要

A method for predicting resistance to BTK inhibitors in patients with chronic lymphocytic leukemia (CLL) enhances the sensitivity of Sanger sequencing and NGS by using wild-type blocking of genes that are relevant for detecting resistance to ibrutinib. Further enhancement of sensitivity can be achieved by using cell-free DNA.

主权项

1. A method for screening and/or monitoring a patient for a BTK inhibitor-resistant mutation, the method comprising:
isolating DNA from a sample selected from bone marrow aspirate (BM), fresh peripheral blood (PB), and tissue obtained from the patient; performing PCR on the isolated DNA to produce amplified DNA while blocking amplification of wild-type DNA in a portion of the isolated DNA that encodes a BTK polypeptide and a portion of the isolated DNA that encodes a PLCγ2 polypeptide; sequencing the amplified DNA in an automated sequencer; and analyzing an output of the automated sequencer to identify mutations in the sequence.