Novel method improves drug resistance screening in myeloid leukemia mutations

A new method has been developed by SciLifeLab researchers for the clinical application of long-read sequencing for resistance mutation screening (BCR-ABL1 tyrosine kinase inhibitors, TKI). The methodology is already being used in a clinical setting for patients undergoing treatment for chronic myeloid leukemia (CML).

“We have recently published a precision medicine study after working for seven years to implement a method to improve the detection of mutations that indicate resistance to drugs that treat chronic myeloid leukemia”, says last author Ola Spjuth (SciLifeLab/UU). 

The research team quickly established processes for registering and transferring samples from the clinic to an academic facility for PacBio single molecule real-time (SMRT) long-read sequencing. Furthermore, they developed an automated analysis pipeline for detecting mutations and implemented an information system comprising features for data management, analysis, and visualization. 

The Uppsala University Hospital, Akademiska Sjukhuset, has already implemented the novel methodology at their clinic. Doctors now have access to more detailed reports on mutations that cause resistance, leading to quicker changes in treatment for patients who develop resistance to drugs such as Imatinib. 

After a validation study to identify resistance mutations by Sanger sequencing, a method for determining the nucleotide sequence of DNA, and long-read sequencing in parallel, the clinical laboratory at Akademiska Sjukhuset switched their routine protocol from using Sanger to long-read sequencing for this application. 

“What I am particularly proud of is the successful collaboration between my research group at UU/SciLifeLab and the SciLifeLab Genomics and Clinical Genomics platforms. We also started a related spin-off company”, he continues.

All developed software is available as open source via GitHub at The project also resulted in the spin-off company Pincer Bio, targeting clinical applications for long-read sequencing.

“This manuscript marks the academic outcome of a long and successful collaboration between my research group (Pharmaceutical Bioinformatics) at Uppsala University, with the SciLifeLab Genomics and Clinical Genomics platform, as well as Uppsala University Hospital”, says Ola Spjuth.

Another relevant impact is the improved decision-making for managing CML patients enabled by the higher sensitivity in detecting emerging TKI resistance mutations. 


Last updated: 2022-09-19

Content Responsible: Johan Inganni(