FLT3 inhibitors in acute myeloid leukemia

Abstract

The fms-like tyrosine kinase 3 (FLT3) plays an important role in both normal and malignant hematopoiesis. Activating mutations in the FLT3 receptor can be detected in approximately 30% of acute myeloid leukemias (AMLs) and are associated with a distinctly poor clinical outcome for patients. There are now several classes of FLT3 inhibitors in development with varying degrees of potency and selectivity for the target, including several in late-phase clinical trials in combination with chemotherapy. Major clinical responses in AML patients receiving single-agent FLT3 inhibitors have been rare, although transient peripheral blood blast reduction is common. Given such biological suggestion and preclinical activity, FLT3 inhibitors hold promise in improving the outcome of patients with mutant FLT3 AML. This review summarizes the current attempts to target this molecule, with emphasis on the validity of the target, the results of the clinical trials evaluating the FLT3 inhibitors in AML, the optimal use of these compounds and the mechanisms of resistance.

Keywords::

• acute myeloid leukemia
• FLT3
• inhibitor
• prognosis
• tyrosine kinase

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.