{"entity":{"id":"flt3","kind":"target","name":"FLT3","aka":[],"tldr":"FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.","summary":"FLT3 is a class III receptor tyrosine kinase, and internal tandem duplications (ITD) or tyrosine kinase domain (TKD) mutations activate it in roughly 25 to 30 percent of acute myeloid leukaemias, with ITD predicting shorter survival. Adding a FLT3 inhibitor to intensive chemotherapy improves survival: midostaurin, gilteritinib and quizartinib are approved, with quizartinib and midostaurin used in the front line and gilteritinib in relapsed disease. Combinations with venetoclax and with menin inhibitors are being tested to deepen and prolong responses. Resistance through emergent TKD mutations, clonal switching and the role of FLT3 inhibitors as maintenance after transplant remain open. For a newcomer: FLT3 is the AML kinase where a targeted pill added to chemotherapy has clearly extended lives.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD135","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD135"}],"tags":["driver","kinase"],"related":["flt3-itd","flt3-tkd"],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["men1703"],"companies":["cullinan-therapeutics"],"institutions":[],"pathways":["aml-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FLT3","role":[],"sources":[],"specificity":"tumour-specific","distribution":"one-type","specificityNote":"Tumour-specific alteration: 2 of 2 label readouts filed under it measure a sequence variant (FLT3-ITD (internal tandem duplication), FLT3-TKD (D835 and I836 tyrosine kinase domain mutations)) absent from normal cells. HPA FLT3: RNA tissue enhanced (bone marrow 5 nTPM, brain 9 nTPM, lymphoid tissue 6 nTPM); blood lineage lineage enriched (dendritic cells 69 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 11 specific cancer types at or above 0.5 (acute myeloid leukemia, hepatocellular carcinoma, gastrointestinal stromal tumor, renal cell carcinoma, myelofibrosis, acute lymphoblastic leukemia and more); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"FLT3-ITD (internal tandem duplication) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=29cdbcfe-497d-4e78-bb7b-2d4acafe8e86","note":"FLT3-ITD-positive"},{"label":"FLT3-TKD (D835 and I836 tyrosine kinase domain mutations) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=11fa3fc9-6776-49a6-b1c1-653f627c3e58","note":"FLT3 mutation-positive (includes TKD)"},{"label":"Human Protein Atlas FLT3 tissue","url":"https://www.proteinatlas.org/ENSG00000122025-FLT3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000122025 associations","url":"https://platform.opentargets.org/target/ENSG00000122025/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:3765","ensembl":"ENSG00000122025","uniprot":"P36888","entrez":"2322","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Rosnet et al, Genomics, 1991, \"Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2004790/","biology":"Class III receptor tyrosine kinase; ITD predicts shorter survival.","whereFound":["Acute myeloid leukaemia"],"targetClass":"kinase","prevalence":[{"cancerId":"aml","pct":"25-30","measure":"FLT3-ITD or TKD","source":"https://www.cbioportal.org/study/summary?id=laml_tcga_pan_can_atlas_2018"}]},"route":"/targets/flt3/","neighbours":{"biomarker":[{"id":"flt3-itd","kind":"biomarker","name":"FLT3-ITD (internal tandem duplication)","route":"/biomarkers/flt3-itd/"},{"id":"flt3-tkd","kind":"biomarker","name":"FLT3-TKD (D835 and I836 tyrosine kinase domain mutations)","route":"/biomarkers/flt3-tkd/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"advanced-systemic-mastocytosis","kind":"cancer","name":"Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)","route":"/cancers/advanced-systemic-mastocytosis/"},{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","route":"/cancers/aml-flt3/"},{"id":"systemic-mastocytosis","kind":"cancer","name":"Systemic mastocytosis","route":"/cancers/systemic-mastocytosis/"}],"drug":[{"id":"fedratinib","kind":"drug","name":"Fedratinib","route":"/drugs/fedratinib/"},{"id":"gilteritinib","kind":"drug","name":"Gilteritinib","route":"/drugs/gilteritinib/"},{"id":"men1703","kind":"drug","name":"MEN1703","route":"/drugs/men1703/"},{"id":"midostaurin","kind":"drug","name":"Midostaurin","route":"/drugs/midostaurin/"},{"id":"pacritinib","kind":"drug","name":"Pacritinib","route":"/drugs/pacritinib/"},{"id":"quizartinib","kind":"drug","name":"Quizartinib","route":"/drugs/quizartinib/"}],"company":[{"id":"aptose","kind":"company","name":"Aptose Biosciences","route":"/companies/aptose/"},{"id":"arog-pharmaceuticals","kind":"company","name":"Arog Pharmaceuticals","route":"/companies/arog-pharmaceuticals/"},{"id":"cullinan-therapeutics","kind":"company","name":"Cullinan Therapeutics","route":"/companies/cullinan-therapeutics/"}],"pathway":[{"id":"aml-signalling","kind":"pathway","name":"Acute myeloid leukaemia (KEGG map)","route":"/pathways/aml-signalling/"},{"id":"menin-kmt2a","kind":"pathway","name":"Menin / KMT2A (HOXA9-MEIS1 axis)","route":"/pathways/menin-kmt2a/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"target":[{"id":"npm1","kind":"target","name":"NPM1 mutation","route":"/targets/npm1/"},{"id":"pkc","kind":"target","name":"Protein kinase C family (PKC)","route":"/targets/pkc/"},{"id":"stat5","kind":"target","name":"STAT5 (STAT5A, STAT5B)","route":"/targets/stat5/"}],"term":[{"id":"eln-risk","kind":"term","name":"ELN 2022 risk classification","route":"/terms/eln-risk/"},{"id":"flt3-itd-allelic-ratio","kind":"term","name":"FLT3-ITD allelic ratio","route":"/terms/flt3-itd-allelic-ratio/"}],"trial":[{"id":"admiral","kind":"trial","name":"ADMIRAL","route":"/trials/admiral/"},{"id":"quantum-first","kind":"trial","name":"QuANTUM-First","route":"/trials/quantum-first/"},{"id":"ratify","kind":"trial","name":"RATIFY (CALGB 10603)","route":"/trials/ratify/"}],"pairing":[{"id":"flt3i-plus-7-3","kind":"pairing","name":"FLT3 inhibitor + intensive chemotherapy","route":"/pairings/flt3i-plus-7-3/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"person":[{"id":"alexander-perl","kind":"person","name":"Alexander E. Perl","route":"/people/alexander-perl/"},{"id":"eunice-wang","kind":"person","name":"Eunice S. Wang","route":"/people/eunice-wang/"},{"id":"hartmut-dohner","kind":"person","name":"Hartmut Döhner","route":"/people/hartmut-dohner/"},{"id":"richard-stone","kind":"person","name":"Richard M. Stone","route":"/people/richard-stone/"}],"paper":[{"id":"paper-admiral-gilteritinib-flt3-nejm-2019","kind":"paper","name":"ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia","route":"/key-papers/paper-admiral-gilteritinib-flt3-nejm-2019/"},{"id":"paper-quantum-first-quizartinib-lancet-2023","kind":"paper","name":"QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML","route":"/key-papers/paper-quantum-first-quizartinib-lancet-2023/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}