[Genetic Mutation Profile and Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia with Mutations...

To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation.

Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method.

Four variables were finally included in our nomogram model after multivariate Cox analysis, and an equation for risk score calculation was obtained, risk score=1.300 2×white blood cell (WBC) (≥18.77×10⁹/L)+1.406 5×CSF3R mutation positive+2.648 9× KMT2A mutation positive+1.012 8×DNA methylation-related genes mutation positive. According to the nomogram model, patients were further divided into low-risk group (score=0, n=46) and high-risk group (score>0, n=95). Prognostic analysis showed that the 5-year LFS rate, 5-year overall survival (OS) rate, and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5%, 97.1%, and 3.5%, while those in patients who received maintenance chemotherapy were 32.9%, 70.5%, and 63.4%, respectively. The differences were statistically significant (all P < 0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However, no corresponding benefit was observed in the low-risk group.

Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R, KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group, allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.