Prognostic impact of ASXL1 mutations in patients with myelodysplastic syndromes and multilineage dysplasia with or without ring sideroblasts

Introduction: The 2016 World Health Organization (WHO) classification of myeloid neoplasms reclassified patients with myelodysplastic syndromes (MDS) with multilineage dysplasia (MLD) based on the presence or absence of ring sideroblasts (RS). We performed this study to validate this change in the context of relevant gene mutations. Methods: WHO-defined MDS and MLD were identified with detailed clinical, cytogenetic and outcomes data. A 32-gene targeted exome sequencing panel was performed on bone marrow samples obtained at diagnosis. Results: Ninety eight patients were included; 59 (60%) MDS-MLD and 39 (40%) MDS-RS-MLD. There were no significant differences in the median overall survival (OS) in the two groups (25 months each, p = 0.6). Among the myeloid-relevant gene mutations, presence of ASXL1 (HR 2.5, p = 0.005) was identified as an adverse prognostic factor in a multivariate analysis. Conclusion: While segregation of MDS-MLD based on RS holds little prognostic relevance, ASXL1 mutational status significantly and independently predicts poor outcomes.