Clinical Information

The FMS-like tyrosine gene (FLT3) codes for a transmembrane receptor/signaling protein (FLT3) of the tyrosine kinase group. Binding of FLT3 ligand to the FLT3 receptor ultimately leads to production of proteins that cause cell growth and inhibit cell death through apoptosis. Recently, variants in FLT3 have been found in some hematopoietic neoplasms and are particularly common in adult acute myeloid leukemia (AML) with an overall incidence of approximately 20% to 30%. The highest genetic variant rates are seen in adult patients with AML and normal- or intermediate-risk cytogenetics and in patients with acute promyelocytic leukemia.

The most common FLT3 variant consists of internal tandem duplication (ITD) of DNA sequences found in exons 14 or 15. In some subgroups of adults with AML, the presence of an FLT3 ITD variant has been found to be an adverse prognostic indicator. The second most common variant is a point alteration in the codon for an aspartate residue (D835) that resides in the activation loop of the FLT3 protein. D835 alterations have been identified in approximately 7% of AML cases but, at this time, it is not clear if the presence of this alteration has any prognostic significance. It is thought that both types of FLT3 variants lead to constitutive (always present, independent of internal or external stimuli) FLT3 activation.

Identification of an FLT3 variant in AML is clinically useful, not only because of the prognostic information it provides, but also because FLT3-inhibitory drugs have shown promise as useful therapeutic agents.