Molecular characteristics of NPM1 mutations in AML patients using targeted NGS

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ABSTRACT Background Acute myeloid leukemia (AML) is a clonal hematopoietic stem cell malignancy characterized by the accumulation of myeloid progenitor cells with arrested differentiation, leading to the suppression of normal hematopoiesis. The disease exhibits significant heterogeneity, with less than 30% five-year overall survival. Nucleophosmin 1 (NPM1) is the most commonly mutated gene in adult AML, found in approximately 25–35% of patients, and is recognized as a distinct subtype by the WHO. Methods The mutational status of NPM1 was assessed using the Oncomine Myeloid research panel on the Ion5S NGS platform (Thermo Fisher Scientific, USA). Results In our AML cohort, NPM1 was the most frequently mutated gene (75%). Indel mutations in the NPM1 gene, frequently resulting in frameshift consequences, show a statistically significant difference in variant allele frequency (VAF) compared to other mutation types. Specifically, NPM1-mutated cases exhibit a VAF that is positively correlated with initial bone marrow (BM) blast counts. Univariate logistic regression analysis reveals that a high VAF is significantly associated with non-complete remission (Non-CR), while a low VAF is significantly associated with complete remission (CR), indicating a statistically significant difference in outcomes (p = 0.012). Conclusion Targeted NGS technology enables the simultaneous analysis of multiple AML-relevant genes, offering a comprehensive mutational profile that supports risk stratification, diagnosis, and personalized treatment. Our findings highlight the significant impact of NPM1 mutations on patient outcomes, revealing their molecular characteristics and their correlation with different clinical parameters.