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FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.
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.
In plain words · FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.
FLT3 is a kinase mutated in about a third of acute myeloid leukaemias, where adding an inhibitor to chemotherapy improves survival.
Class III receptor tyrosine kinase; ITD predicts shorter survival.
6 products aim at FLT3: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: FLT3-ITD (internal tandem duplication) label threshold; FLT3-TKD (D835 and I836 tyrosine kinase domain mutations) label threshold; Human Protein Atlas FLT3 tissue; Open Targets ENSG00000122025 associations
First described 1991. 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". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
Class III receptor tyrosine kinase; ITD predicts shorter survival.
RNA: tissue enhanced (bone marrow 5 nTPM, brain 9 nTPM, lymphoid tissue 6 nTPM), detected in some normal tissues. Blood: lineage enriched (dendritic cells 69 nTPM).
No normal tissue stained high.
RNA cancer enhanced: Breast Invasive Carcinoma 3 pTPM.
No cancer sample stained medium or high.
HPA FLT3 tissue · HPA FLT3 pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | 25-30% | FLT3-ITD or TKD | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
A second JAK inhibitor for myelofibrosis that works after ruxolitinib fails; it carries a boxed warning for a rare brain toxicity (Wernicke encephalopathy) so thiamine is checked.
A single pill that beats salvage chemotherapy for relapsed FLT3-mutated AML, and the backbone of the triplets now being tested in frontline disease.
MEN1703 is an experimental small molecule (kinase inhibitor) from Ryvu Therapeutics in phase 2 trials for hodgkin lymphoma, aimed at FLT3.
The first drug to improve survival in FLT3-mutated AML, added to standard chemotherapy: median survival went from about two years to more than six.
The JAK inhibitor for myelofibrosis patients whose platelet counts are too low for ruxolitinib.
Quizartinib is a more selective FLT3 blocker that, added to chemotherapy, roughly doubled median survival in the highest-risk FLT3 subtype.
QuANTUM-First gave FLT3-ITD AML patients a second front-line targeted option and showed that continuing a FLT3 inhibitor as long-term maintenance, including after transplant, pays off. Quizartinib was approved for this indication in 2023. Head-to-head data against midostaurin are lacking, and the design leaves open how much of the benefit came from maintenance.
ADMIRAL showed that a targeted oral drug can beat chemotherapy outright in relapsed AML, and made gilteritinib the standard bridge to transplant for FLT3-mutated relapse. Its success also underpinned FLT3 inhibitor use in first-line combinations. Resistance through FLT3-independent clones and RAS pathway mutations limits durability without transplant.
Query for this target: (TITLE:"FLT3" OR ABSTRACT:"FLT3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FLT3, not a curated reading list.
Shares Midostaurin, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Acute myeloid leukaemia (KEGG map), Systemic mastocytosis and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.
Shares Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.
Shares Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Small-molecule kinase inhibitors and the tags driver, kinase.
Shares Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Receptor tyrosine kinase activation, Small-molecule kinase inhibitors and the tags driver, kinase.