Avaliação da composição da ancestralidade genética por snp array em pacientes com neoplasia mielodisplásica

Abstract

Myelodysplastic neoplasms (MDS) comprise a heterogeneous group of hematologic disorders characterized by the ineffective maturation of progenitor cells in the bone marrow and a risk of progression to acute myeloid leukemia (AML), with a strong correlation to age due to the accumulation of mutations and genomic instability. In this context, the study of genetic ancestry and ethnic-regional differences is fundamental, as it allows for the correlation of inherited variants with clinical phenotypes, demonstrating a significant influence on the incidence and clinical characteristics of MDS. For this reason, this study aims to assess the composition of genetic ancestry in patients with MDS in order to investigate possible associations between genetic ancestry and the clinical characteristics of the disease. In this retrospective study, samples were analyzed from 94 patients diagnosed with MDS between 2020 and 2025 and from 94 participants with no history of previous cancer. The analyses were performed using the SNP array technique, also known as microarray genotyping, which was carried out using the AxiomTM Precision Medicine Diversity Array (PMDA) panel (Thermo Fisher Scientific, USA). The results were submitted for further analysis after undergoing quality control. Four ancestral clusters were identified: EUR (European), AFR (African), EAS (East Asian), and AMR (Native American). Ancestry analysis was then performed using the ADMIXTURE software. The results showed a predominance of European ancestry in the cohort. Specifically, the data revealed significant correlations between the genetic profile and the patients’ clinical or demographic characteristics: more severe cases of the disease had a higher proportion of Asian ancestry, while Native American ancestry was more pronounced in individuals from rural areas and in patients with hemoglobin levels below 8 g/dL. Finally, it was found that patients with hypercellular bone marrow had a higher proportion of European ancestry. Therefore, it can be concluded that genetic ancestry may influence certain clinical characteristics of MDS, playing a key role in better stratification of the disease and leading to improved individualized treatment selection.