Mutational and genomic landscape of acute myeloid leukemia: Insights from a South Asian targeted next-generation sequencing cohort

Objectives

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy, yet comprehensive genomic data from South Asian populations remain limited. Population-specific mutation profiling is critical for accurate risk stratification and optimal use of targeted therapies. This study characterizes the genomic landscape of AML in a South Asian cohort using next-generation sequencing (NGS). Material and Methods: We analyzed 167 AML patients with pathogenic variants using the Myeloid HAEM DNA-RNA NGS panel (Oncomine Myeloid Research Assay) (Thermo Fisher Scientific, Waltham, Massachusetts), covering 40 DNA-based genes and 29 fusion transcripts. Variants were interpreted according to American Society of Hematology (ASH)/Association for Molecular Pathology/European Hematology Association (EHA) recommendations and classified using the OncoKB Tier system, which stratifies alterations based on their therapeutic, diagnostic, and prognostic relevance into Tier I (strong clinical significance), Tier II (potential clinical significance), and Tier III (unknown clinical significance). Mutation frequencies, co-mutation patterns, and age distributions of genetic aberrations were also analyzed.