Difference in gene mutation profile in patients with refractory/relapsed versus newly diagnosed acute myeloid leukemia based on targeted next-generation sequencing.

We have reported the genetic mutation profile in previously untreated acute myeloid leukemia (AML) patients using a targeted NGS screening method. In this study, we evaluated the characteristics and prognostic significance of gene mutations in refractory/relapsed (R/R) AML patients by comparing their gene mutation spectrum to those newly diagnosed. The frequencies of tumor suppressor mutations were increased, while the mutation frequencies of nucleophosmin and spliceosome complex were decreased in relapsed AML. The frequency of FLT3-ITD mutation was increased, while that of CEBPA biallelic mutation decreased in refractory AML. Activated signaling mutations predicted a lower complete remission rate. FLT3-ITD mutation predicted an inferior overall survival after relapse. DNMT3A mutation predicted an inferior relapse-free survival in R/R AML. These findings may shed light on the molecular mechanism study of leukemia refractory or relapse and provide new guidance for the dynamic risk assessment of AML.