FLT3 Mutation Analysis

Whole blood, bone marrow or cell pellet

3-5 mL whole blood or 1-2 mL bone marrow

3 mL whole blood or 1 mL bone marrow

Lavender-top (EDTA) tube or green-top (sodium heparin) tube

Mutations in the FLT3 gene are common mutations in acute myeloid leukemia (AML). This assay detects internal tandem duplication (ITD) mutations and mutations in the tyrosine kinase domain (TKD) of FLT3. Presence of these mutations in AML provide prognostic information and can aid in the determination of therapeutic regimen.

This PCR assay is capable of detecting a mutant cell population with a sensitivity of 5 mutant cells per 100.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Polymerase chain reaction (PCR); restriction enzyme digest; capillary electrophoresis

FLT3 is a receptor tyrosine kinase (RTK) that dimerizes on binding its ligand, the cytokine FLT3 ligand (FL), which then undergoes autophosphorylation, and transduces signals downstream (STAT, AKT, ERK) that promote proliferation and survival. Activating mutations of FLT3 are common mutations found in AML. A particular form of FLT3 is mutated by duplicating coding sequence derived from the juxtamenbrane domain inserted in tandem (internal tandem duplication (ITD). These FLT3-ITD mutations result in the constitutive activation of the tyrosine kinase function. Patients with FLT3-ITD mutations have increased relapse rates and reduced overall survival. Point mutations in the activation loop of the kinase domain, most commonly at the residue Asp 835 (D835), also known as tyrosine kinase domain (TKD) mutations, also result in the constitutive activation of the FLT3 kinase. Signaling from FLT3-TKD mutations does not appear as abnormal, and the prognostic impact appears to be less severe when compared with ITD mutations (FLT3-ITD mutations are found in ~23% of AML cases, whereas TKD mutations are found in 7%).