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.