An NGS based MRD evaluation from acute myeloid leukemia patients

Introduction Measurable residual disease (MRD) is a prognostic factor for acute myeloid leukemia (AML). A next‐generation sequencing (NGS) based MRD panel was developed and the results were validated. Methods The NGS sequencing data was collected from 1003 Chinese AML patients. Results The sequencing data from 586 newly diagnosed AML patients showed that NRAS mutation was most common (20.8%), followed by NPM1 (19.4%), FLT3‐ITD (18.5%), and DNMT3A (15.4%). NPM1 and FLT3‐ITD mutations were less in Chinese than in Caucasian AML patients, and the result of KRAS mutation was opposite. A new panel named “AML NGS‐MRD hot‐spot panel” was designed, containing 178 hot‐spot exons from 52 mutated genes and only 62.8 Kb in size. With this hot‐spot panel, 92.5% newly diagnosed AML patients were found to carry ≥1 mutations. To verify the performance of this panel, additional 205 newly diagnosed AML patients and 212 post‐treatment AML patients were evaluated, and the hot‐spot panel achieved a similar detection rate (91.2% for newly diagnosed AML patients and 89.2% for post‐treatment AML patients). Finally, this study found that the mutation frequencies of signaling pathway genes (e.g., KRAS, NRAS, FLT3‐ITD, KIT) were significantly reduced in post‐treatment AML. Conclusion The “AML NGS‐MRD hot‐spot panel” detected the mutations from relapsed AML patients with minimal panel size, and was a reliable and cost‐effective panel for AML patients.