Genetic Mutation Signature for Relapse Prediction in Normal Karyotype Acute Myeloid Leukemia

Background: Risk stratification for normal karyotype acute myeloid leukemia (NK-AML) remains unsatisfactory owing to the high incidence of leukemia relapse. This study aimed to evaluate the role of gene mutations and clinical characterization in predicting the relapse of patients with NK-AML.

Methods: A prognostic system for NK-AML was constructed based on gene mutations, measurable residual disease (MRD), and clinical characteristics. A panel of gene mutations was explored using next-generation sequencing. The least absolute shrinkage and selection operator, and nomogram algorithm were used to build a genomic mutation signature (GMS) and nomogram (GMSN) model that combines GMS, MRD, and clinical factors to predict relapse in 347 patients with NK-AML from four centers.

Results: Patients with GMS-high had a higher 5-year incidence of relapse than those with GMS-low (P < 0.001). The 5-year incidence of relapse was also higher in patients with GMSN-high than those with GMSN-intermediate and -low (P < 0.001). The 5-year disease-free survival and overall survival rates were lower in patients with GMSN-high than in those with GMSN-intermediate and -low (P < 0.001) as confirmed by training and validation cohorts.

Conclusions: This study illustrated the potential of GMSN as a predictor of NK-AML relapse.

No relevant conflicts of interest to declare.