FLT3 Gene: Function, Mutations, and Role in AML | NCBI, UniProt, ClinVar

FLT3 (Fms Related Receptor Tyrosine Kinase 3) encodes a class III receptor tyrosine kinase that regulates hematopoiesis, particularly the survival, proliferation, and differentiation of hematopoietic stem and progenitor cells. The receptor is activated by binding of the FLT3 ligand (FL), leading to dimerization and downstream signaling via PI3K/AKT, RAS/MAPK, and STAT5 pathways. FLT3 is frequently mutated in acute myeloid leukemia (AML), with internal tandem duplications (ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain (TKD) being the most common activating alterations.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• PI3K/AKT signaling pathway

• RAS/MAPK signaling pathway

• JAK/STAT signaling pathway (STAT5)

• FLT3 signaling in hematopoiesis

• Acute myeloid leukemia (AML) pathway

FLT3 (CD135) is a 993-amino acid transmembrane receptor tyrosine kinase expressed primarily on hematopoietic stem and progenitor cells. The extracellular domain contains five immunoglobulin-like domains, followed by a single transmembrane helix, a juxtamembrane domain, and a split intracellular tyrosine kinase domain. Upon FL binding, FLT3 dimerizes and autophosphorylates, activating downstream signaling cascades that promote cell survival, proliferation, and differentiation. Mutations in FLT3, particularly ITD and TKD, are among the most common genetic alterations in AML and are targets for tyrosine kinase inhibitors such as midostaurin, gilteritinib, and quizartinib.