Prognostic value of ASXL1 mutations in patients with myelodysplastic syndromes and acute myeloid leukemia: A meta-analysis

Abstract

Additional sex combs-like 1 (ASXL1) mutations, a hotspot in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), have been frequently reported for their potential prognostic value, but the results are controversial. Therefore, a meta-analysis was performed. Databases, including PubMed, Embase, and Cochrane Library, were searched for relevant studies published up to January 13, 2022. STATA v16.0 software was used to calculate the combined hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and AML transformation. Subgroup analysis was used to explore the effects of the grouping factors on heterogeneity.Ten studies on ASXL1 mutations and the prognosis of MDS were selected. Our results indicate that ASXL1 mutations have an adverse prognostic impact on OS (HR = 1.68,95%CI:1.45-1.94, p < .0001) and AML transformation (HR = 2.20,95% CI:1.68-2.87, p < .0001). The results for different age groups were not significantly different (HR = 1.87,95% CI: 1.31-2.67; HR = 1.62,95% CI:1.35-2.07). Ten studies covering 5816 patients with AML were included. The pooled HR for OS was 1.37 (95% CI:1.20-1.56, p < .0001). ASXL1 mutations were especially associated with a poorer OS in the subgroup aged ≥60 years (HR = 2.86, 95% CI:1.34-6.08, p = .006); when considering cytogenetically normal AML (CN-AML), the HR was 1.78(95% CI:1.27-2.49, p = .001). This meta-analysis indicates an independent, adverse prognostic impact of ASXL1 mutations in patients with MDS and AML, which also applies to patients with CN-AML. Age was a risk factor for patients with AML and ASXL1 mutations but not for patients with MDS.

Keywords: ASXL1 mutations; acute myeloid leukemia; age; meta-analysis; myelodysplastic syndromes.