Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1.
Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways
Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation (By similarity).
Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2. Interacts with RNF115 and RNF126 (By similarity)
(Microbial infection) Interacts with human cytomegalovirus protein UL7
Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in granulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia
The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase.
The activity of the mutant kinase can be stimulated further by FLT3LG binding
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue.
Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to FLT3, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 19
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT01846624 | Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults, AML (Adult) With 11q23 (MLL) Abnormalities, AML (Adult) With Del (5q), AML (Adult) With Inv (16) (p13; q22), AML (Adult) With t (16;16) (p13; q22), AML (Adult) With t (8; 21) (q22; q22), Secondary AML (Adult), Untreated AML (Adult) | Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia | PHASE2 | TERMINATED |
| NCT02624570 | Acute Myeloid Leukemia (AML) With, FLT3 Mutation, Internal Tandem Duplication (ITD) or Tyrosine Kinase Domain (TKD) | Midostaurin Access Program for Newly Diagnosed FLT3 (ITD or TKD) Mutated AML Adult Patients Eligible for Standard Induction and Consolidation Chemotherapy | N/A | NO_LONGER_AVAILABLE |
| NCT03379727 | Acute Myeloid Leukemia | Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Maintenance Monotherapy in Patients With Newly-diagnosed FMS-like Tyrosine 3 (FLT3) Kinase Receptor-mutated Acute Myeloid Leukemia. | PHASE3 | COMPLETED |
| NCT03324243 | Relapsed/Refractory FLT3-mutated AML | A Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia | PHASE2 | WITHDRAWN |
| NCT03591510 | FLT3-mutated Acute Myeloid Leukemia | A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT00779480 | Acute Myelogenous Leukemia (AML) | Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Study of KW-2449 in Acute Myelogenous Leukemia (AML) (Protocol Number: 2449-US-002) | PHASE1 | TERMINATED |
| NCT02474290 | Acute Myeloid Leukemia, Hematopoietic Stem Cell Transplantation | Sorafenib for Prophylaxis of Leukemia Relapse in Allo-HSCT Recipients With FLT3-ITD Positive AML | PHASE2, PHASE3 | COMPLETED |
| NCT06667973 | Acute Myeloid Leukemia, FLT3 Gene Mutation, Adult AML, Diagnosis | Efficacy of Gilteritinib in Combination With FLAI as Induction Therapy of FLT3-positive Acute Myeloid Leukemia | PHASE2 | NOT_YET_RECRUITING |
| NCT03047083 | Acute Myeloid Leukemia (AML) | Treatment Patterns and Key Healthcare Resource Use in Acute Myeloid Leukemia (AML) With or Without FMS-like Tyrosine Kinase-3 (FLT3) Mutation Study Based on Retrospective Chart Review | N/A | COMPLETED |
| NCT03250338 | Relapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations | Study Investigating the Efficacy of Crenolanib With Chemotherapy vs Chemotherapy Alone in R/R FLT3 Mutated AML | PHASE3 | COMPLETED |