AML-258: Next-Generation Sequencing Used to Detect Multiple Mutations in Acute Myeloid Leukemia Patients

Context New molecular tecniques allow the characterization of clonal heterogeneity in acute myeloid leukemia (AML) at diagnosis or during treatment. In the past decades, the mutational landscape identified in AML has become more diverse and is allowing identification of new prognostic factors. Objective To develop an in-house next-generation sequencing method that can be used to assess the mutational status of the patient at diagnosis and during treatment. Design The sequencing method screens for 8 regions in 5 genes involved in pathogenesis and progression of AML: FLT3, IDH1, IDH2, DNMT3A, and RUNX1. Setting Screening for these mutations will permit the stratification of patients into risk group at diagnosis, and using the method for minimal residual assesment will permit the development of personalised treatment programs. Patients or other participants A number of 51 patients diagnosed with AML in the Molecular Biology Laboratory of the Fundeni Clinical Institute between 2017 and 2019 were tested using an in-house sequencing method. Every patient included was tested at diagnosis for the presence of a reciprocal translocation and for presence of FLT3-ITD. Interventions For all patients, standard treatment was started after diagnosis. Bone marrow transplant was recommended and performed for only three patients. Main outcome measures To determine the functionality of the method for mutation detection in AML patients, as well as to familiarize the physicians with these mutations and to use them in treatment decisions. Results From the 51 patients included, 20 patients (39%) harboured one or more mutations in the genes tested. Mutations in DNMT3A and IDH2 were found to be more frequent. In 4 out of 20 patients (20%) mutations in DNMT3A and FLT3-ITD+ concurred. Survival was poor, and only 3 patients are still in follow-up: one patient harboring FLT3-ITD and RUNX1, one with mutations in RUNX1, and one with mutations in IDH2. Conclusions The method developed to test for somatic mutation has proven to be useful and has a lower cost than a commercial kit. Also, the method can be improved by adding new testing targets. Funding We gratefully acknowledge the funding from the project Competitiveness Operational Programme (COP), MyeloAL-EDiaProT, Contract 149/26.10.2016.