The importance of FLT3 mutational analysis in acute myeloid leukemia

Abstract

Activating mutations in FMS-like tyrosine kinase 3 (FLT3), including internal tandem duplications (ITDs) and tyrosine kinase domain (TKD) mutations, are common in patients with acute myeloid leukemia (AML). FLT3-ITD is a negative prognostic factor that remains prognostically relevant even after intensive chemotherapy and/or stem cell transplant. FLT3 testing was historically viewed as being purely prognostic; however, with the advent of FLT3 inhibitors, it will likely be seen as both prognostic and predictive. The multikinase inhibitor midostaurin, in combination with chemotherapy, is the first targeted agent to significantly prolong survival in patients with newly diagnosed FLT3-mutated AML and was recently approved by health authorities. Recently, the European LeukemiaNet recommended FLT3 testing (both TKD and ITD) for all patients with AML, with results required within 3 days. The need for optimized, multigene platform testing incorporating FLT3 mutations will increase as knowledge of interactions between FLT3 and other myeloid-relevant mutations grows.

Keywords:

• AML
• FLT3 testing
• prognostic
• predictive marker
• FLT3 tyrosine kinase inhibitor

Acknowledgments

Editorial assistance was provided by Katherine Mills-Lujan, PhD, CMPP, and Pamela Tuttle, PhD, CMPP, of ArticulateScience LLC, and was funded by Novartis Pharmaceuticals Corporation. This work was supported by the National Center for Advancing Translational Sciences under CTSA Grant Number KL2 TR000136. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Potential conflict of interest

Disclosure forms provided by the author is available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1399312.