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The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (<i>FLT3</i>-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common <i>FLT3</i>-TKD mutations (D835Y, D835H, D835V, D835E). Twenty-two diagnostic samples, six donor controls, and a commercial D835Y positive control were tested using a commercial Bio-rad^® ddPCR assay. All known variants were identified, and no false positives were detected in the wild-type control (100% specificity and sensitivity). The assays achieved a limit of detection suitable for MRD testing at 0.01% variant allelic fraction. Serial samples from seven intensively-treated patients with <i>FLT3</i>-TKD variants at diagnosis were tested. Five patients demonstrated clearance of <i>FLT3</i>-TKD clones, but two patients had <i>FLT3</i>-TKD persistence in the context of primary refractory disease. In conclusion, ddPCR is suitable for the detection and quantification of <i>FLT3</i>-TKD mutations in the MRD setting; however, the clinical significance and optimal management of MRD positivity require further exploration.