Abstract
BACKGROUND AND AIMS: Nucleophosmin (NPM1) gene mutations occur in approximately 30%-35% of individuals with an initial diagnosis of acute myeloid leukemia (AML). Mutations in this gene have been reported in 50%-60% of AML patients with a normal karyotype. These mutations help to distinguish clinicopathological and molecular features, setting them apart as a unique subset within the heterogeneous landscape of AML. In the present study, we investigated the frequency and clinical impact of NPM1 (mut) in 100 newly diagnosed adult Syrian patients with AML-normal karyotype (NK) using direct sequencing. METHODS: We analyzed 100 AML-NK patients using direct sequencing to assess the prevalence and clinical impact of NPM1 mutations, as well as the co-occurrence of FLT3-ITD and DNMT3A mutations. RESULTS: Our results revealed that the prevalence of NPM1 (mut) was 22% among the patients; 86.4% of these mutations were type A (NM_002520.5:c.860-863dupTCTG), while 13.6% were de novo mutations (c.863_864insCCTG, p.Trp288CysfsTer12), (c.861_862dup, p.Trp288SerfsTer13), and (c.863_864insCCGG, p.Trp288CysfsTer12). Among our patients, 22% exhibited NPM1 (mut), with 7% also harboring FLT3-ITD (mut) and 2% having DNMT3A (mut). The presence of NPM1 (mut) was correlated with a statistically significant increase in bone marrow blast percentage (p = 0.017). Notably, patients with NPM1 (mut) displayed significantly higher mortality rates, with 72.7% succumbing to the disease compared to 29.5% of patients without NPM1 (mut) (p < 0.001). Furthermore, our results showed that when the overall survival (OS) time exceeded 8.35 months, the likelihood of NPM1 wild-type status was greater. CONCLUSION: The evaluation of NPM1 (mut) and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.