The Clinical Impact of NPM1 Mutations and the Effect of Concurrent Mutations in Acute Myeloid Leukemia: Unraveling the Prognostic Significance

Abstract

Background and AimsNucleophosmin (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 NPM1mut in 100 newly diagnosed adult Syrian patients with AML‐normal karyotype (NK) using direct sequencing.MethodsWe 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.ResultsOur results revealed that the prevalence of NPM1mut 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 NPM1mut, with 7% also harboring FLT3‐ITDmut and 2% having DNMT3Amut. The presence of NPM1mut was correlated with a statistically significant increase in bone marrow blast percentage (p = 0.017). Notably, patients with NPM1mut displayed significantly higher mortality rates, with 72.7% succumbing to the disease compared to 29.5% of patients without NPM1mut (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.ConclusionThe evaluation of NPM1mut 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.