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

Tyrosine-protein kinase Fms-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase that is predominantly expressed on the surface of hematopoietic stem and progenitor cells (UniProt P36888). It plays a pivotal role in the early stages of hematopoiesis, regulating the proliferation, survival, and differentiation of multipotent stem cells through the activation of signaling cascades such as the PI3K/Akt, MAPK/ERK, and JAK/STAT pathways (PubMed: 29074092). FLT3 is one of the most frequently mutated genes in acute myeloid leukemia (AML), with internal tandem duplications (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD) occurring in approximately 30% of patients (StatPearls: NBK546645). These mutations lead to constitutive activation of the receptor, driving aggressive leukemic cell growth and contributing to poor clinical outcomes. Therapeutic intervention typically involves small-molecule tyrosine kinase inhibitors (TKIs), such as midostaurin and gilteritinib, which target the intracellular kinase domain to inhibit autophosphorylation (FDA: 2017/2018). Despite their efficacy, clinical challenges include the development of secondary resistance mutations and managing off-target toxicities like QTc prolongation and myelosuppression (PubMed: 32154247).

Other names

FLK-2STK-1CD135Stem cell tyrosine kinase 1Fetal liver kinase 2

Small-molecule inhibition of the tyrosine kinase activity by competing with ATP for the binding site, thereby blocking downstream signaling pathways such as PI3K/Akt and MAPK/ERK.