African Journal of Laboratory Medicine

Background: In patients with acute myeloid leukaemia (AML), pathogenic variants in the additional sex combs-like 1 (ASXL1) gene confer poor prognosis and are frequently involved in clonal haematopoiesis of indeterminate potential, with increasing prevalence with advancing age.
Objective: We determined the prevalence of ASXL1 variants in an AML cohort and general elderly population in central South Africa.
Methods: The study included 40 participants with de novo AML and 100 elderly participants (≥ 65 years). Polymerase chain reactions and Oxford nanopore sequencing of ASXL1 exon 12 were performed on all samples between 01 October 2023 and 30 September 2024.
Results: Of the 40 AML participants, 25 (62.5%) were women, with a median age of 42 years. ASXL1 mutations were detected in 5%. In total, 248 ASXL1 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: The prevalence of ASXL1 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: Routine ASXL1 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.