Fms-like tyrosine kinase 3 (FLT3) (FLT3)

Fms-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase primarily expressed on hematopoietic stem and progenitor cells, where it plays a critical role in regulating cell survival, proliferation, and differentiation (UniProt P36888). In its wild-type state, FLT3 is activated by the FLT3 ligand, triggering downstream signaling cascades including the PI3K/AKT, RAS/MAPK, and STAT5 pathways (PubMed: 28213375). Mutations in the FLT3 gene, most commonly internal tandem duplications (ITD) or point mutations in the tyrosine kinase domain (TKD), lead to constitutive, ligand-independent activation of the receptor (NIH: National Cancer Institute). These mutations are found in approximately 30% of adult patients with acute myeloid leukemia (AML) and are associated with a poor prognosis, high relapse rates, and decreased overall survival (StatPearls: FLT3 Inhibitors). Therapeutic strategies focus on small-molecule tyrosine kinase inhibitors (TKIs) that block the ATP-binding site of the receptor, thereby inhibiting oncogenic signaling (PubMed: 30611161). While first-generation inhibitors like midostaurin are multi-kinase inhibitors, second-generation agents like gilteritinib and quizartinib offer greater potency and selectivity, though clinical challenges remain regarding the emergence of secondary resistance mutations (PubMed: 32106111).

Other names

CD135Fetal liver kinase 2FLK-2Stem cell tyrosine kinase 1STK-1

Small molecule inhibition of the intracellular tyrosine kinase domain, preventing autophosphorylation and downstream signaling pathways such as PI3K/AKT, MAPK/ERK, and STAT5 (PubMed: 30611161).