{"entity":{"id":"bcr-abl1-t315i","kind":"biomarker","name":"BCR::ABL1 T315I","aka":["T315I","BCR-ABL T315I","ABL1 T315I","T315I mutation","gatekeeper mutation CML"],"tldr":"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.","asOf":"2026-09-23","links":[{"label":"SCEMBLIX prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e33001e7-3650-42b1-ae56-cddb5c43aa2b"},{"label":"Iclusig prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16d804b6-4957-43ee-b18c-3b36ec37c5ac"}],"tags":["biomarker","cml","resistance"],"related":["bcr-abl1-transcript"],"cancers":["cml","cml-chronic-phase","cml-advanced-phase","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["ponatinib","asciminib"],"companies":[],"institutions":[],"pathways":[],"terms":["abl1-kinase-domain-mutations","gatekeeper-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"bcr-abl","measurement":"sequencing-variant","scoringRule":{"text":"The ABL1 c.944C>T (p.T315I) substitution in the BCR::ABL1 kinase domain by Sanger or next-generation sequencing of blood or marrow RNA.","quote":"Ph+ CML in CP with the T315I mutation.","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e33001e7-3650-42b1-ae56-cddb5c43aa2b","sourceLabel":"SCEMBLIX prescribing information"},"thresholds":[{"value":"T315I-positive","drugId":"ponatinib","cancerId":"cml","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=16d804b6-4957-43ee-b18c-3b36ec37c5ac","quote":"As monotherapy in Ph+ ALL for whom no other kinase inhibitors are indicated or T315I-positive Ph+ ALL.","status":"current","note":"The Iclusig label also covers chronic, accelerated and blast phase CML with the T315I mutation."},{"value":"T315I mutation, chronic phase","drugId":"asciminib","cancerId":"cml-chronic-phase","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e33001e7-3650-42b1-ae56-cddb5c43aa2b","quote":"Ph+ CML in CP with the T315I mutation.","status":"current"}],"tests":["foundationone-heme"],"assays":[],"companionDiagnostics":[],"forPatient":"If your leukaemia's BCR::ABL1 level has risen and sequencing finds T315I, the usual tablets will no longer work; ponatinib or asciminib are the two approved options and a transplant may be discussed. Testing for the mutation is done from a blood sample whenever response is lost."},"route":"/biomarkers/bcr-abl1-t315i/","neighbours":{"biomarker":[{"id":"bcr-abl1-transcript","kind":"biomarker","name":"BCR::ABL1 transcript (Philadelphia chromosome, quantitative PCR)","route":"/biomarkers/bcr-abl1-transcript/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"cml","kind":"cancer","name":"Chronic myeloid leukaemia (CML)","route":"/cancers/cml/"},{"id":"cml-advanced-phase","kind":"cancer","name":"Chronic myeloid leukaemia, accelerated and blast phase","route":"/cancers/cml-advanced-phase/"},{"id":"cml-chronic-phase","kind":"cancer","name":"Chronic myeloid leukaemia, chronic phase","route":"/cancers/cml-chronic-phase/"}],"drug":[{"id":"asciminib","kind":"drug","name":"Asciminib","route":"/drugs/asciminib/"},{"id":"ponatinib","kind":"drug","name":"Ponatinib","route":"/drugs/ponatinib/"}],"term":[{"id":"abl1-kinase-domain-mutations","kind":"term","name":"BCR::ABL1 kinase domain mutations (T315I and others)","route":"/terms/abl1-kinase-domain-mutations/"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"}],"target":[{"id":"bcr-abl","kind":"target","name":"BCR::ABL1 (Philadelphia chromosome)","route":"/targets/bcr-abl/"}]}}