{"entity":{"id":"flt3-tkd","kind":"biomarker","name":"FLT3-TKD (D835 and I836 tyrosine kinase domain mutations)","aka":["FLT3-TKD","FLT3 TKD","FLT3 D835","FLT3 D835Y","FLT3 I836","FLT3 tyrosine kinase domain mutation"],"tldr":"FLT3-TKD mutations are point changes in the kinase's activation loop, found in about 7 percent of acute myeloid leukaemias. Midostaurin and gilteritinib labels cover them; quizartinib's does not.","summary":"D835 substitutions and I836 deletions in exon 20 activate FLT3 without the duplication seen in ITD; their prognostic weight is neutral in ELN 2022. The LeukoStrat CDx assay detects D835 and I836 alongside ITD, which is why midostaurin (newly diagnosed 'FLT3 mutation-positive' AML) and gilteritinib (relapsed or refractory 'with a FLT3 mutation') cover TKD mutations, while quizartinib is labelled for FLT3-ITD only. TKD mutations, especially D835, also arise as resistance to type II inhibitors such as quizartinib and sorafenib.","asOf":"2026-09-23","links":[{"label":"XOSPATA prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5ff59aa-9c0d-49a8-9053-1f179b482383"}],"tags":["biomarker","flt3"],"related":["flt3-itd"],"cancers":["aml","aml-flt3"],"sections":[],"technologies":[],"targets":[],"drugs":["midostaurin","gilteritinib","quizartinib"],"companies":[],"institutions":[],"pathways":[],"terms":["gatekeeper-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"flt3","measurement":"sequencing-variant","scoringRule":{"text":"A FLT3 D835 or I836 mutation in the tyrosine kinase domain by the LeukoStrat CDx assay or sequencing of blood or marrow.","quote":"ITD mutations and TKD mutations D835 and I836","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"FLT3 mutation-positive (includes TKD)","drugId":"midostaurin","cancerId":"aml-flt3","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=11fa3fc9-6776-49a6-b1c1-653f627c3e58","quote":"Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive as detected by an FDA-approved test","status":"current"},{"value":"FLT3 mutation (includes TKD), relapsed or refractory","drugId":"gilteritinib","cancerId":"aml-flt3","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5ff59aa-9c0d-49a8-9053-1f179b482383","quote":"relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test","status":"current"}],"tests":["foundationone-heme","neotype-profiles"],"assays":["flt3-leukostrat"],"companionDiagnostics":[{"device":"LeukoStrat CDx FLT3 Mutation Assay","maker":"Invivoscribe Technologies","drugs":["midostaurin","gilteritinib"],"indication":"Acute Myelogenous Leukemia - Peripheral Blood or Bone Marrow","pma":"P160040 (04/28/2017)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"A FLT3-TKD mutation means midostaurin can be added to your first chemotherapy and gilteritinib is on label if the leukaemia returns; quizartinib is not approved for TKD-only disease. A TKD mutation that appears later, during treatment with quizartinib, is a sign of resistance and a reason to switch."},"route":"/biomarkers/flt3-tkd/","neighbours":{"biomarker":[{"id":"flt3-itd","kind":"biomarker","name":"FLT3-ITD (internal tandem duplication)","route":"/biomarkers/flt3-itd/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","route":"/cancers/aml-flt3/"}],"drug":[{"id":"gilteritinib","kind":"drug","name":"Gilteritinib","route":"/drugs/gilteritinib/"},{"id":"midostaurin","kind":"drug","name":"Midostaurin","route":"/drugs/midostaurin/"},{"id":"quizartinib","kind":"drug","name":"Quizartinib","route":"/drugs/quizartinib/"}],"term":[{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"}],"target":[{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/"}]}}