Additional sex combs-like 1 variants in an acute myeloid leukaemia and a general elderly cohort in central South Africa

Abstract

Background: ) gene confer poor prognosis and are frequently involved in clonal haematopoiesis of indeterminate potential, with increasing prevalence with advancing age. Objective: variants in an AML cohort and general elderly population in central South Africa. Methods: exon 12 were performed on all samples between 01 October 2023 and 30 September 2024. Results: variants were detected in 68 of the 100 elderly participants aged 65-88 years (mean 71 years). Variants in the coding regions included synonymous (58.4%) and missense (41.6%) variants. Benign variants were detected in 29% of the elderly participants, while variants of uncertain significance were present in 2%, each with a variant allele frequency of ≥ 20%. No pathogenic or likely pathogenic variants were identified. Conclusion: exon 12 variants in our AML cohort was consistent with international data. Variants in the elderly population were very prevalent; however, with no actionable variants capable of driving clonal expansion, clonal haematopoiesis of indeterminate potential was not detected. The variants of uncertain significance at allele frequencies of ≥ 2% likely suggest a clonal haematopoietic process. What this study adds: testing in all AML patients is not recommended in our resource-limited setting. Testing should be individualised according to its potential clinical impact, using high-throughput sequencing with clinically relevant variant classification.