# BCR::ABL1 T315I

Source: https://onco.cc/biomarkers/bcr-abl1-t315i/  
OnCo record `bcr-abl1-t315i` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

T315I is the gatekeeper mutation in the ABL1 kinase that defeats imatinib, dasatinib, nilotinib and bosutinib. Ponatinib and asciminib are the two drugs approved for it.

## Summary

The threonine-to-isoleucine change at the gatekeeper residue removes a hydrogen bond the first- and second-generation inhibitors need and adds steric bulk. It is detected by Sanger or next-generation sequencing of the kinase domain when BCR::ABL1 levels rise. Ponatinib (Iclusig) is labelled for T315I-positive CML in any phase and T315I-positive Ph+ ALL; asciminib (Scemblix), which binds the myristoyl pocket rather than the ATP site, is labelled for Ph+ CML in chronic phase with the T315I mutation at a higher dose. Allosteric plus ATP-site combinations are in trials for compound mutations.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: T315I; BCR-ABL T315I; ABL1 T315I; T315I mutation; gatekeeper mutation CML
- Tags: biomarker; cml; resistance

## Sources

- SCEMBLIX prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e33001e7-3650-42b1-ae56-cddb5c43aa2b
- Iclusig prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16d804b6-4957-43ee-b18c-3b36ec37c5ac

## Connected records

- biomarkers: [BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)](https://onco.cc/biomarkers/bcr-abl1-transcript/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Chronic myeloid leukaemia (CML)](https://onco.cc/cancers/cml/), [Chronic myeloid leukaemia, accelerated and blast phase](https://onco.cc/cancers/cml-advanced-phase/), [Chronic myeloid leukaemia, chronic phase](https://onco.cc/cancers/cml-chronic-phase/)
- drugs: [Asciminib](https://onco.cc/drugs/asciminib/), [Ponatinib](https://onco.cc/drugs/ponatinib/)
- terms: [BCR::ABL1 kinase domain mutations (T315I and others)](https://onco.cc/terms/abl1-kinase-domain-mutations/), [On-target resistance mutations (gatekeeper, solvent-front, compound)](https://onco.cc/terms/gatekeeper-mutation/)
- targets: [BCR::ABL1 (Philadelphia chromosome)](https://onco.cc/targets/bcr-abl/)

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