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

Background And Aims: Nucleophosmin ) 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 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 mutations, as well as the co-occurrence of -ITD and mutations.

Results: Our results revealed that the prevalence of 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 , with 7% also harboring and 2% having . The presence of was correlated with a statistically significant increase in bone marrow blast percentage ( = 0.017). Notably, patients with displayed significantly higher mortality rates, with 72.7% succumbing to the disease compared to 29.5% of patients without ( < 0.001). Furthermore, our results showed that when the overall survival (OS) time exceeded 8.35 months, the likelihood of wild-type status was greater.

Conclusion: The evaluation of 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.