Characterisation of mutations in cytogenetically normal acute myeloid leukaemiapatients with triple-negative FLT3-ITD/ NPM1/CEBPA subgroup using targeted next-generation sequencing

Genec aberraons play a pivotal role in acute myeloid leukaemia (AML) pathogenesis and clinical outcomes, with mutaons in key genes such as NPM1, FLT3, and CEBPA well-established markers for the disease prognosis.Despite advancements in molecular diagnoscs, a comprehensive analysis of the mutaonal landscape in AML is sll needed using advanced techniques.This study aimed to analyse the mutaonal landscape of cytogenecally normal AML (CN-AML) with triple-negave FLT3-ITD/NPM1/CEBPA subgroup using targeted NGS techniques.Targeted next-generaon sequencing (NGS) was employed to comprehensively explore the mutaonal spectrum of CN-AML in a cohort of 14 paents.In this study, six putave pathogenic or likely pathogenic variants, as well as seven variants of uncertain significance (VUS), were detected in nine CN-AML paents.Among these paents, a single mutaon was observed in six cases, two mutaons in one case, and three mutaons in two cases each.DNMT3A and RUNX1 were present in three cases each, followed by SRSF2 and NRAS, which were found in two cases each.Addionally, CEBPA, TET2, TP53, and U2AF1 were each observed in one case.Targeted NGS analysis revealed a heterogeneous mutaonal spectrum in CN-AML paents with recurrent alteraons, highlighng their potenal impact on disease progression.These findings improve our understanding of the genec landscape of CN-AML and may contribute to refining prognosc classificaon and risk straficaon.