Fms-related receptor tyrosine kinase 3 (FLT3) (FLT3)

Fms-related receptor tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase that is essential for the normal development and proliferation of hematopoietic stem and progenitor cells (UniProt: P36888). Upon binding its ligand, FLT3 homodimerizes and activates intracellular signaling cascades, including the PI3K/AKT, RAS/MAPK, and JAK/STAT pathways, which promote cell survival and growth (NCBI Gene: 2322). In the context of oncology, FLT3 is one of the most frequently mutated genes in acute myeloid leukemia (AML), occurring in approximately 30% of cases (StatPearls: NBK542280). The most common mutations are internal tandem duplications (ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain (TKD), both of which result in constitutive, ligand-independent activation of the receptor (PubMed: 29077305). Because these mutations are associated with high relapse rates and poor overall survival, FLT3 has become a primary therapeutic target. Modern treatment strategies involve the use of FLT3 inhibitors, such as midostaurin and gilteritinib, which are designed to block the kinase activity and induce apoptosis in leukemic blasts (PubMed: 30612135).

Other names

CD135Fetal liver kinase 2 (FLK-2)Stem cell tyrosine kinase 1 (STK-1)FL cytokine receptor

Small-molecule inhibition of the intracellular tyrosine kinase domain, which prevents ATP binding and subsequent autophosphorylation, thereby blocking downstream oncogenic signaling pathways such as PI3K/AKT, MAPK/ERK, and STAT5 (PubMed: 30612135).