FLT3 Mutation Detection

Initial Prognostication in AML
FLT3 ITD and TKD Mutation Detection 3001161
Method: Polymerase Chain Reaction

Genomic DNA is extracted and amplified in multiplex with primers targeting FLT3 mutations in AML

  • FLT3 mutation detection by polymerase chain reaction (PCR) amplification of exon 14 ITDs and D835
  • PCR products are EcoRV-digested and analyzed by capillary electrophoresis
  • ITDs are reported with a signal ratio and D835 variants as Detected or Not Detected
NPM1 Mutation Detection by RT-PCR, Quantitative 3000066
Method: Quantitative Reverse-Transcription Polymerase Chain Reaction
CEBPA Mutation Detection 2004247
Method: Polymerase Chain Reaction/Sequencing
IDH1 and IDH2 Mutation Analysis, exon 4 2006444
Method: Polymerase Chain Reaction/Sequencing

FLT3 mutations have been identified in hematologic neoplasms, particularly in 20-30% of acute myeloid leukemia (AML). FLT3 internal tandem duplication (ITD) mutations have been associated with an unfavorable outcome. FLT3 tyrosine kinase domain mutations affecting codon D835 are also common (7%) but have a less-clear prognostic significance. Early mutation identification may provide better prognostication and aid in the determination of the most effective therapeutic regimen.

Indications for Ordering

  • Refine classification and determine prognosis in patients with AML.
  • Determine FLT3 mutational status in relapsed AML.
  • Aid in selection of appropriate chemotherapy regimen.
  • Not intended for minimal residual disease monitoring.

Disease Overview

Treatment Issues

  • 50% of cases are cytogenetically normal AML (CN-AML) and are considered to be intermediate risk.
  • Mortality varies significantly among patients within the intermediate risk group.
  • Mutational testing may help in AML prognostication.
    • Presence of mutations may alter therapeutic decisions.

Genetics

Structure/Function

FLT3

  • ITDs on exon 14/15; D835 mutation on exon 20
  • Tyrosine kinase receptor regulates cell survival and maturation.

Last Update: March 2019