Prognostic Impact of FLT3, NPM1 and CEBPA Mutations in Cytogenetically Normal Acute Myeloid Leukemia

Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly half of adult AML cases and demonstrates significant clinical heterogeneity. Cytogenetics alone is insufficient for risk stratification, and molecular markers such as FLT3, NPM1, and CEBPA have emerged as key prognostic determinants. This study evaluated the frequency and prognostic impact of FLT3-ITD, FLT3-D835, NPM1, and CEBPA mutations in CN-AML patients. We retrospectively analyzed 55 CN-AML patients diagnosed at a tertiary center (September 2012–2013). Molecular profiling was performed using PCR-based methods. Overall survival (OS) was assessed using Kaplan–Meier analysis and log-rank testing. Mutation frequencies were: FLT3-ITD % 12.7, FLT3-D835 1.8%, NPM1 20%, and CEBPA 14.5%. Complete remission was achieved in % 63.6 of patients. FLT3-ITD mutations were associated with significantly shorter OS (p=0.004), whereas FLT3-ITD(-)/NPM1(+) status correlated with improved OS (p=0.0032). No significant differences in remission rates were observed among subgroups. These findings confirm the prognostic relevance of FLT3 and NPM1 mutations in CN-AML and sup-port routine molecular profiling to guide risk-adapted therapeutic strategies.

Keywords: Acute myeloid leukemia, FLT3, Prognosis