FLT3 Mutation Analysis, Varies (LAB9777)

FMS-like tyrosine kinase 3 (FLT3) is an enzyme-linked cell surface receptor expressed by hematopoietic progenitors and is mutated in approximately 30% of patients with acute myeloid leukemia (AML). Over 80% of FLT3 mutations are in-frame internal tandem duplications (ITDs) involving exons 14 or 15, disrupting the autoinhibitory juxtamembrane domain and leading to constitutive activation. FLT3-ITD mutations can be detected by polymerase chain reaction and capillary electrophoresis (PCR-CE) with a sensitivity of 1%-5% and a turnaround time of two to three days. This method also yields an estimate of the relative abundance of mutant and wild-type alleles, reported as an allelic ratio.

• FLT3 mutation analysis by PCR-CE is not recommended for minimal residual disease (MRD) assessment due to limited sensitivity and the fact that FLT3 mutations can be lost in patients with persistent or relapsed disease.
• FLT3 mutation analysis by PCR-CE is generally not indicated in cases of myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), or acute lymphoblastic leukemia (ALL), where FLT3 mutations are rare.

• PCR for FLT3-ITD should be performed for all patients with new and relapsed AML, as targetable mutations may be gained or lost throughout the course of the disease.

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2. Schuurhuis GJ, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018 Mar 22;131(12):1275-1291. doi: 10.1182/blood-2017-09-801498.
3. Heuser M, et al. 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2021 Dec 30;138(26):2753-2767. doi: 10.1182/blood.2021013626.