Fms-like tyrosine kinase 3 receptor internal tandem duplication mutant (FLT3-ITD)

The Fms-like tyrosine kinase 3 receptor internal tandem duplication mutant (FLT3-ITD) is a mutated form of the FLT3 receptor, a class III receptor tyrosine kinase normally expressed on hematopoietic progenitor cells[1][3][5]. The ITD mutation consists of in-frame duplications, typically located within the juxtamembrane domain, resulting in constitutive (ligand-independent) activation of the receptor and aberrant cell signaling[1][3][5]. This leads to increased cell proliferation, survival, and impaired differentiation, contributing to oncogenesis in acute myeloid leukemia (AML)[1][3][5]. FLT3-ITD mutations occur in about 20–30% of AML cases and are associated with higher relapse rates and poorer survival compared to FLT3 wild type[1][3][5][9]. Several small molecule FLT3 kinase inhibitors (e.g., midostaurin, gilteritinib) have been developed to specifically target and inhibit constitutive kinase activity in FLT3-ITD-positive AML[6]. The presence, allele ratio, and length of the FLT3-ITD mutation serve as important biomarkers for risk stratification and therapeutic decision-making in AML patients[9]. The primary therapeutic challenge remains drug resistance and off-target toxicity associated with FLT3 inhibitors.

Other names

FLT3 internal tandem duplication mutantFLT3-ITDFms-related tyrosine kinase 3 ITD mutantCD135 internal tandem duplication mutant

Inhibition of constitutive kinase activity; Inhibition of downstream pro-survival and proliferative signaling pathways (PI3K/AKT, RAS/MAPK, STAT5); Induction of apoptosis in leukemia cells