What is AML?
Acute myeloid leukemia (AML) is an aggressive and highly proliferative form of cancer where the bone marrow makes abnormal myeloblasts (a type of white blood cell). AML is the most common form of leukemia in adults and progresses quickly if left untreated.
With the widespread use of genetic testing in AML, a number of targeted therapies have been approved in the past few years and transformed AML into an active development space. While these recent approvals demonstrate the enthusiasm for targeted therapies, significant opportunity remains for improving patient outcomes.
AML is a highly heterogenous disease driven by multiple mutations. The most common driver mutations in AML occur in the gene FLT3 (FMS-like tyrosine kinase 3) and are found in approximately 33% of all AML patients. Chemotherapy offers limited benefits in treating cancer cells harboring FLT3 mutations.
FLT3 mutations lead to constitutive activation of the tyrosine kinase function, making FLT3 inhibition an attractive drug target in AML patients. Adding a FLT3 inhibitor to standard chemotherapy has been shown to produce longer lasting benefits compared to chemotherapy alone.
A polyclonal disease, multiple FLT3 mutations have been identified in subjects, including internal tandem duplications (ITD), mutations in the tyrosine kinase domain (TKD), and variant mutations. FLT3 mutations are generally regarded as poor prognostic markers in AML and a number of FLT3 mutations confer resistance to targeted inhibitors.