<i>FLT3</i> internal tandem duplications in acute myeloid leukemia: mechanism of formation and clinical significance

This review presents the FLT3 gene structure and the working principle of the FLT3 protein coded by the gene, details the molecular mechanisms of FLT3 internal tandem duplication formation, the detailed structure and localization of tandem duplications in the FLT3 gene. Modern methods of FLT3-ITD diagnosis are described: fragment analysis, which provides an opportunity to estimate the allelic ratio, and next-generation sequencing, which allows for the study of the character of duplicated fragments and the localization of tandem duplications. This work presents the results of recent studies on the clinical significance of FLT3-ITD in acute myeloid leukemia with a normal karyotype and in the combination of FLT3-ITD with recurrent cytogenetic aberrations, as well as the results of studies showing the influence of the character of duplicated fragments and the location of FLT3-ITD insertion on survival rates. The main types of FLT3-inhibitors, their mechanism of action and clinical efficacy are described. Modern possibilities of FLT3-ITD monitoring and its practical significance for predicting the outcome of acute myeloid leukemia are presented.