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June 29, 2026Genome MedicineOpen Access

Dual functional genomics reveals a broad and convergent landscape of asciminib resistance in BCR::ABL1

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Authors

ISIvan SokirniyZYZeyu YangJPJustin Pritchard

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Overview

Randomized trial identifies mutations linked to asciminib resistance in CML, suggesting new monitoring strategies.

Key Points

  • The study aims to map the resistance mutations to asciminib in CML and understand their interactions.
  • Employed dual functional genomics approach using CML cell line models
  • Conducted high-throughput adenosine base editing screen to identify resistance hotspots
  • Developed a FRET biosensor to measure conformational states of BCR::ABL1.
  • Identified 279 asciminib resistance mutations across SH3, SH2, and kinase domains
  • Uncovered strong epistatic interaction between SH3 mutation V73A and kinase mutation Y253H
  • Demonstrated that resistance mutations destabilize the inactive conformation of the ABL1 kinase.

Cite This Study

Sokirniy et al. (2026) studied this question.

synapsesocial.com/papers/6a420b08f91bb43ea919230bhttps://doi.org/10.1186/s13073-026-01679-x
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