Flt3, also known as FMS-like tyrosine kinase 3, is a type III receptor tyrosine kinase expressed almost exclusively in the hematopoietic compartment [5]. Its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. Activation of FLT3 leads to autophosphorylation and initiates signal transduction cascades like STAT5, MAPK, and AKT, mediating cell survival, proliferation, and differentiation of hematopoietic progenitor cells [4,5].

Mutations of the Flt3 gene occur in approximately 30% of all acute myeloid leukemia (AML) cases [1]. The internal tandem duplication (ITD) in the juxtamembrane domain is the most common type (about 25% of all AML cases), while mutations in the tyrosine kinase domain (FLT3-TKD, about 7-10% of cases) are less frequent [1,3]. FLT3-ITD is a driver mutation associated with high leukemic burden, increased relapse, and poor prognosis in AML patients [1,2]. Multiple small-molecule inhibitors of FLT3 signaling have been developed, with midostaurin and gilteritinib approved in the United States [2]. However, resistance to these inhibitors through secondary FLT3 mutations, upregulation of parallel pathways, and extracellular signaling remains a challenge [2].

In conclusion, Flt3 plays a crucial role in hematopoietic cell survival, proliferation, and differentiation. Its mutations, especially FLT3-ITD, are significant in AML, conferring a poor prognosis. The development of FLT3 inhibitors has improved treatment for AML patients with Flt3 mutations, but resistance remains a major obstacle. Research on Flt3, including through genetic models, is essential for understanding AML and developing more effective therapies [1-10].