Field of application

Measurable residual disease (MRD) detection for FLT3-ITD mutations and NPM1 mutations in patients with acute myeloid leukemia (AML). AML is a clinically and molecularly heterogeneous hematopoietic malignancy with high initial remission rates. The detection of measurable residual disease (MRD) has emerged as an independent prognostic marker to identify high-risk relapse patients and to evaluate the response to treatment. Common genetic mutations in cytogenetically normal (CN)-AML such as Nucleophosmin (NPM1) mutations and Flt-3 internal tandem duplication (Flt3-ITD) are used as valuable markers to quantify molecular MRD. For NPM1, type A mutation (c.860_863dupTCTG) accounts for 70–80% of cases while mutations B (c.863_864insCATG) and D (c.863_864insCCTG) together account for 15–20% and NPM1 mutations are a very stable marker during follow-up and disease relapse. Flt3-ITD mutations may be lost or acquired over the disease course, which implies that it should not be used a single molecular marker for MRD monitoring. Both diagnostic and follow-up sample are required for analysis. For the Flt3-ITD MRD assay, exons 14 and 15 of the FLT3 gene were amplified by PCR. For detection of all NPM1 mutations, exon 12 of the NPM1 gene was amplified.

Analysis

• FLT3-ITD: Pindel

• NPM1: samtools mpileup

Only RUO, no reimbursement