Functional properties of exon 17 KIT mutations in pediatric CBF AML predict for inferior outcome and enhanced response to tyrosine kinase inhibition: a report from the children …

Introduction: KIT mutations are detected in approximately 20-30% of core binding factor (CBF, t(8;21) and inv(16)/t(16;16)) AML and have been associated with outcome and response to tyrosine kinase inhibitors (TKI). Mutations tend to localize to 2 regions- the receptor's kinase activation loop in exon 17 (E17) and a region of the extracellular domain in exon 8 (E8). The prognostic significance of the 2 mutations has varied in previous series. In this analysis, the functional significance of E8) and E17 KIT mutations in vitro and their response to TKIs were evaluated. We hypothesized that activating variants might be associated with inferior clinical outcome and be more susceptible to KIT-targeted agents.