Pharmacological impact of FLT3 mutations on receptor activity and responsiveness to tyrosine kinase inhibitors

• Structural aspects of the FLT3 receptor in signalling. Clonal evolution mutants. Recurrent mutations and its regulation signalling cascade drug therapy. Acute myelogenous leukaemia (AML) is an aggressive blood cancer characterized by rapid proliferation immature myeloid blast cells, resulting a high mortality rate. The 5-year overall survival rate for AML patients approximately 25%. Circa 35% all carry mutation gene which have poor prognosis. Targeting tyrosine kinase has become treatment strategy possessing mutations. most common are internal tandem duplications (ITD) within exon 14 single nucleotide polymorphism (SNP) that leads to point D835 domain (TKD). Variations ITD sequence occurrence other lead ligand-independent activation create difficulties developing personalized therapeutic strategies overcome observed mutation-driven resistance. Midostaurin quizartinib inhibitors (TKIs) with inhibitory efficacy against FLT3-ITD, but exhibit limited clinical impact. In this review, we focus on structural correlate those consequences molecular responsiveness towards therapies targeting FLT3-ITD positive AML.